Can the Minimum Protamine Dose to Neutralize Heparin at the Completion of Cardiopulmonary Bypass be Significantly Lower than the Conventional Practice?

Systemic anticoagulation with heparin during cardiopulmonary bypass (CPB) should be neutralized by protamine administration to restore normal hemostasis. However, protamine has potentially serious side effects and excessive protamine can cause increased postoperative bleeding. Thus, our goal is to appropriately dose protamine at the completion of CPB to neutralize heparin so that neither residual heparin nor excessive protamine is present. We performed a retrospective study of 216 patients who underwent cardiac surgery to search for a safe minimum protamine dose (PD) when measuring heparin concentration (HC). In addition, we developed a formula to determine PD using total heparin dose (THD) and CPB time without measuring HC. When protamine-to-heparin ratio (P-to-H) is set at 1 mg protamine to 100 international unit (IU) heparin in HMS Plus Hemostasis Management System (HMS), we determined that 75% of the calculated total PD is a safe minimum PD to sufficiently neutralize circulating heparin after CPB. On average, this translates into either .37 mg protamine/100 IU heparin of THD or .54 mg/100 IU of the first heparin bolus. The formula we developed to calculate PD without measuring HC can provide a PD that strongly agrees with the safe minimum PD when measuring HC. The safe minimum PD to neutralize circulating heparin after CPB can be significantly lower than conventional dosing practices. Reduction of PD may decrease the risk of postoperative bleeding and protamine-related adverse events. Based on our data, we decreased P-to-H in HMS to examine whether it is possible to reduce PD further than the safe minimum PD determined in this study.

Improved Estimation of Total Blood Volume Can Provide a Reliable Prediction of Dilutional Hematocrit and Oxygen Delivery during Cardiopulmonary Bypass.

Optimal oxygen delivery during cardiopulmonary bypass (CPB) for open heart surgery is crucial to protect organ function, improve outcomes, and reduce hospital stay. Effective preparation for optimal oxygen delivery during CPB is dependent on a reliable estimation of total blood volume (TBV) to accurately predict dilutional hematocrit (Hct) and calculate indexed oxygen delivery (iDO2). Unreliable estimation of TBV is a major reason for inaccurate prediction of dilutional Hct and iDO2. We performed a retrospective study of 113 patients who underwent cardiac surgery to compare the accuracy of predicted versus measured Hct and iDO2. We used four conventional methods of TBV estimation: 1) weight based A; 70 mL/kg for all patients, 2) weight based B; 70 mL/kg for males and 65 mL/kg for females, 3) Allen's formula, and 4) Nadler's formula. We found that TBV estimated by Allen's formula predicted dilutional Hct better than the other three. However, all four methods overestimate TBV when Hct is low and underestimate when Hct is high, suggesting that TBV is dependent on Hct in addition to body size and gender. Our analysis indicates that two individuals with the same body size and gender can have different TBV depending on Hct. We revised Allen's formula by adding a component that adjusts TBV depending on Hct to provide a more accurate prediction of dilutional Hct and iDO2.

Effect of sex on nadir hematocrit and rates of acute kidney injury in coronary artery bypass.

OBJECTIVE: Findings from a large multicenter experience showed that sex influenced the relationship between low nadir hematocrit and increased risk of acute kidney injury after cardiac surgery. We explored whether sex-related differences persisted among patients undergoing isolated coronary artery bypass grafting. METHODS: We undertook a prospective, observational study of 17,363 patients without dialysis (13,137 male: 75.7%; 4226 female: 24.3%) undergoing isolated coronary artery bypass grafting between 2011 and 2016 across 41 institutions in the Perfusion Measures and Outcomes registry. Odds ratios between nadir hematocrit and stage 2 or 3 acute kidney injury were calculated, and the interaction of sex with nadir hematocrit was tested. The multivariable, generalized, linear mixed-effect model adjusted for preoperative and intraoperative factors and institution. RESULTS: Median nadir hematocrit was 22% among women and 27% among men (P < .001). Women were administered a greater median net prime volume indexed to body surface area (407 vs 363 mL/m2) and more red blood cell transfusions (55.5% vs 24.3%; both P < .001). Acute kidney injury was higher among women (6.0% vs 4.3%, P < .001). There was no effect of sex on the relationship between nadir hematocrit and acute kidney injury (P = .67). Low nadir hematocrit was inversely associated with acute kidney injury (adjusted odds ratios per 1-unit increase in nadir hematocrit 0.96; 95% confidence interval, 0.93-0.98); this effect was similar across sexes and independent of red blood cell transfusions. CONCLUSIONS: We found no sex-related differences in the effect of nadir hematocrit on acute kidney injury after isolated coronary artery bypass grafting. However, the strong inverse relationship between anemia and acute kidney injury across sexes suggests the importance of reducing exposure to low nadir hematocrit.

Is Conventional Bypass for Coronary Artery Bypass Graft Surgery a Misnomer?

Although recent trials comparing on vs. off-pump revascularization techniques describe cardiopulmonary bypass (CPB) as "conventional," inadequate description and evaluation of how CPB is managed often exist in the peer-reviewed literature. We identify and subsequently describe regional and center-level differences in the techniques and equipment used for conducting CPB in the setting of coronary artery bypass grafting (CABG) surgery. We accessed prospectively collected data among isolated CABG procedures submitted to either the Australian and New Zealand Collaborative Perfusion Registry (ANZCPR) or Perfusion Measures and outcomes (PERForm) Registry between January 1, 2014, and December 31, 2015. Variation in equipment and management practices reflecting key areas of CPB is described across 47 centers (ANZCPR: 9; PERForm: 38). We report average usage (categorical data) or median values (continuous data) at the center-level, along with the minimum and maximum across centers. Three thousand five hundred sixty-two patients were identified in the ANZCPR and 8,450 in PERForm. Substantial variation in equipment usage and CPB management practices existed (within and across registries). Open venous reservoirs were commonly used across both registries (nearly 100%), as were "all-but-cannula" biopassive surface coatings (>90%), whereas roller pumps were more commonly used in ANZCPR (ANZCPR: 85% vs. PERForm: 64%). ANZCPR participants had 640 mL absolute higher net prime volumes, attributed in part to higher total prime volume (1,462 mL vs. 1,217 mL) and lower adoption of retrograde autologous priming (20% vs. 81%). ANZCPR participants had higher nadir hematocrit on CPB (27 vs. 25). Minimal absolute differences existed in exposure to high arterial outflow temperatures (36.6°C vs. 37.0°C). We report substantial center and registry differences in both the type of equipment used and CPB management strategies. These findings suggest that the term "conventional bypass" may not adequately reflect real-world experiences. Instead of using this term, authors should provide key details of the CPB practices used in their patients.

An In-Vitro Study Comparing the GME Handling of Two Contemporary Oxygenators.

Gaseous microemboli (GME) are a potential complication of cardiopulmonary bypass (CPB). Though it is difficult to prove that GME is the only major cause of neurological deficits, it may increase the chance of post-operative cognitive dysfunction if not removed. The objectives of this research were to compare LivaNova-Sorin Inspire (Inspire) oxygenator with a Medtronic arterial filter to the Medtronic Fusion (Fusion) oxygenator with and without a Medtronic arterial filter based on each system's ability to handle GME. The Inspire and Fusion systems were evaluated in vitro. GME handling was observed by introducing air in the sampling manifold connected to the venous return at a 60 mL bolus or 1 liter per minute (LPM). The emboli detection and classification (EDAC) system measured GME preand post-oxygenator/arterial filter. The Inspire with a filter was able to remove a statistically significant greater amount of total emboli per second during the 60 mL bolus and 1 LPM tests than the Fusion with and without an arterial filter. The Inspire with an arterial filter was more efficient in removing GME during a 60 mL bolus and 1 LPM than the Fusion and Fusion with an arterial filter. However, the Fusion with an arterial filtered performed better than the Fusion system without the arterial filter.

The Relationship between Intra-Operative Transfusions and Nadir Hematocrit on Post-Operative Outcomes after Cardiac Surgery.

Uncertainty exists regarding the optimal strategy for the management of anemia in the setting of cardiac surgery. We sought to improve our understanding of the role of intra-operative hematocrit (HCT) and transfusions on peri-operative outcomes following cardiac surgery. A total of 18,886 patients undergoing on-pump cardiac surgery were identified from a multi-institutional registry including surgical and perfusion data. Patients were divided into four groups based on their intra-operative nadir HCT (<21 or ≥21) and whether or not they received intra-operative red blood cell (+RBC or -RBC) transfusions. Outcomes were adjusted for the Society of Thoracic Surgeons predicted risk of mortality (PROM), pre-operative HCT, and medical center. Regardless of nadir HCT cohort, those who received a transfusion had higher PROM relative to patients who did not receive a transfusion. The mean PROM was significantly higher among those HCT ≥21 + RBC (5.3%) vs. HCT ≥ 21 - RBC (1.9%), p < .001. Similarly, the PROM was significantly higher among HCT <21 + RBC (5.1%) vs. those HCT <21 - RBC (3.1%), p < .001. Adjusted outcomes demonstrated an increased impact of RBC transfusions on adverse outcomes irrespective of nadir HCT including stroke (p < .001), renal failure (p < .001), prolonged ventilation (p < .001), and mortality (p < .001). This study demonstrates that transfusions have a more profound effect on post-operative cardiac surgery outcomes than anemia.

Report from AmSECT's International Consortium for Evidence- Based Perfusion Consensus Statement: Minimal Criteria for Reporting Cardiopulmonary Bypass-Related Contributions to Red Blood Cell Transfusions Associated With Adult Cardiac Surgery.

Gaps remain in our understanding of the contribution of bypass-related practices associated with red blood cell (RBC) transfusions after cardiac surgery. Variability exists in the reporting of bypass-related practices in the peer-reviewed literature. In an effort to create uniformity in reporting, a draft statement outlining proposed minimal criteria for reporting cardiopulmonary bypass (CPB)- related contributions (i.e., RBC data collection/documentation, clinical considerations for transfusions, equipment details, and clinical endpoints) was presented in conjunction with the American Society of ExtraCorporeal Technology's (AmSECT's) 2014 Quality and Outcomes Meeting (Baltimore, MD). Based on presentations and feedback from the conference, coauthors (n = 14) developed and subsequently voted on each proposed data element. Data elements receiving a total of 4 votes were dropped from further consideration, 5-9 votes were considered as "Recommended," and elements receiving ≥10 votes were considered as "Mandatory." A total of 52 elements were classified as mandatory, 16 recommended, and 14 dropped. There are 8 mandatory data elements for RBC data collection/documentation, 24 for clinical considerations for transfusions, 13 for equipment details, and 7 for clinical endpoints. We present 52 mandatory data elements reflecting CPB-related contributions to RBC transfusions. Consistency of such reporting would offer our community an increased opportunity to shed light on the relationship between intra-operative practices and RBC transfusions.

Greater Volume of Acute Normovolemic Hemodilution May Aid in Reducing Blood Transfusions After Cardiac Surgery.

BACKGROUND: Perioperative red blood cell transfusions (RBC) are associated with increased morbidity and mortality after cardiac surgery. Acute normovolemic hemodilution (ANH) is recommended to reduce perioperative transfusions; however, supporting data are limited and conflicting. We describe the relationship between ANH and RBC transfusions after cardiac surgery using a multi-center registry. METHODS: We analyzed 13,534 patients undergoing cardiac surgery between 2010 and 2014 at any of the 26 hospitals participating in a prospective cardiovascular perfusion database. The volume of ANH (no ANH, <400 mL, 400 to 799 mL, ≥ 800 mL) was recorded and linked to each center's surgical data. We report adjusted relative risks reflecting the association between the use and amount of ANH and the risk of perioperative RBC transfusion. Results were adjusted for preoperative risk factors, procedure, body surface area, preoperative hematocrit, and center. RESULTS: The ANH was used in 17% of the patients. ANH was associated with a reduction in RBC transfusions (RRadj [adjusted risk ratio] 0.74, p < 0.001). Patients having 800 mL or greater of ANH had the most profound reduction in RBC transfusions (RRadj 0.57, p < 0.001). Platelet and plasma transfusions were also significantly lower with ANH. The ANH population had superior postoperative morbidity and mortality compared with the no ANH population. CONCLUSIONS: There is a significant association between ANH and reduced perioperative RBC transfusion in cardiac surgery. Transfusion reduction is most profound with larger volumes of ANH. Our findings suggest the volume of ANH, rather than just its use, may be an important feature of a center's blood conservation strategy.

Impact of Ultrafiltration on Kidney Injury After Cardiac Surgery: The Michigan Experience.

BACKGROUND: This study examines the relationship between the use and volume of conventional ultrafiltration (CUF) and the risk of acute kidney injury (AKI) after isolated on-pump coronary artery bypass graft surgery. METHODS: A total of 6,407 consecutive patients underwent isolated on-pump coronary artery bypass graft surgery between 2010 and 2013 at 21 medical centers participating in the PERFusion Measures and Outcomes (PERForm) registry. We assessed the effect of CUF use on AKI and other postoperative sequelae using a generalized linear mixed-effect model with a logit link. We also modeled the effect of increasing volume of CUF per weight on AKI, and tested for any modification by a patient's preoperative kidney function. RESULTS: Patients having CUF were more likely to have diabetes, vascular disease, chronic obstructive pulmonary disease, congestive heart failure, history of a myocardial infarction, or an intraaortic balloon pump (p < 0.05). They had lower preoperative and nadir hematocrits, creatinine clearance, and ejection fraction (p < 0.05). Patients exposed to CUF had higher adjusted risk of AKI (adjusted odds ratio, 1.36; p = 0.002), although similar rates of death, stroke, and reoperation for bleeding (p > 0.05). The risk of AKI was modified by a patient's preoperative kidney function (p < 0.0004). Among patients with a creatinine clearance of less than 99.6 mL/min (95% confidence interval, 67.6 to 137.5), increasing volume of CUF was associated with a higher risk of AKI. CONCLUSIONS: Patients exposed to CUF had a higher adjusted risk of AKI. Clinical teams should consider lower volumes of CUF among patients with low creatinine clearance to minimize the risk of AKI.

Report from AmSECT's International Consortium for Evidence-Based Perfusion: American Society of Extracorporeal Technology Standards and Guidelines for Perfusion Practice: 2013.

UNLABELLED: One of the roles of a professional society is to develop standards and guidelines of practice as an instrument to guide safe and effective patient care. The American Society of Extracorporeal Technology (AmSECT) first published its Essentials for Perfusion Practice, Clinical Function: Conduct of Extracorporeal Circulation in 1993. The International Consortium for Evidence-Based Perfusion (ICEBP), a committee within AmSECT, was tasked with updating this document in 2010. The aim of this report is to describe the method of development and content of AmSECT's new professional standards and guidelines. The ICEBP committee independently evaluated and provided input regarding the current "Essentials and Guidelines." Structural changes were made to the entire document, and a draft document was developed, presented, and circulated to the AmSECT Board of Directors and broader membership for comment. Informed by these reviews, a revised document was then presented to the Society for a membership vote. The final document consists of 15 areas of practice covered by 50 Standards and 38 Guidelines (see Appendix 1) with the first standard focusing on the development of institutional protocols to support their implementation and use. A majority of the membership voted to accept the document (81.2% of the voting membership accepting, 18.8% rejecting). After an audit of the balloting process by AmSECT's Ethics Committee, the results were reported to the membership and the document was officially adopted on July 24, 2013. The Standards and Guidelines will serve as a useful guide for cardiac surgical teams that wish to develop institution-specific standards and guidelines to improve the reliability, safety, and effectiveness of adult cardiopulmonary bypass. The ICEBP recognizes that the development of a Standards and Guidelines statement alone will not change care. Safe, reliable, and effective care will be best served through the development and implementation of institutional protocols based on these standards. AmSECT's Standards and Guidelines for Perfusion Practice reflect the changing landscape of our profession as we work toward a safer and optimal provision of cardiopulmonary bypass for all our patients as well as a work environment that is supportive of delivering this care. KEYWORDS: standards, guidelines, cardiopulmonary bypass, perfusion, cardiac surgery.

Validation of a perfusion registry: methodological approach and initial findings.

Although regional and national registries exist to measure and report performance of cardiac surgical programs, few registries exist dedicated to the practice of cardiopulmonary bypass (CPB). We developed and implemented a cardiovascular perfusion registry (Perfusion Measures and outcomes [PERForm] Registry) within the structure of the Michigan Society of Thoracic and Cardiovascular Surgeons (MSTCVS) to improve our understanding of the practice of CPB. The PERForm Registry comprises data elements describing the practice of CPB. Fourteen medical centers within MSTCVS have voluntarily reported these data on procedures in which CPB is used. We validated the case count among procedures performed between January 1, 2011 to December 31, 2011, and validated the values among 20 fields at three medical centers. We queried database managers at all 14 medical centers to identify the infrastructure that contributed to best overall data collection performance. We found that 98% of all records submitted to the PERForm and 95% of those submitted to the Society of Thoracic Surgeons (STS) matched. We found quite favorable agreement in our audit of select fields (95.8%). Those centers with the most favorable performance in this validation study were more likely to use electronic data capture, have a perfusionist as the STS database manager, and have involvement of the STS database manager in the PERForm or STS databases. We successfully and accurately collected data concerning cardiovascular perfusion among 14 institutions in conjunction with the MSTCVS. Future efforts will focus on expanding data collection to all MSTCVS participating institutions as well as more broadly outside of Michigan.

International pediatric perfusion practice: 2011 survey results.

New cardiopulmonary bypass devices and new innovative methods are frequently reported in the literature; however, the actual extent to which they are adopted into clinical practice is not well known. We distributed an electronic survey to 289 domestic and international pediatric congenital surgery centers in an effort to measure attributes of current clinical practice. The survey consisted of 107 questions relating to program demographics, equipment, and techniques. Responses were received from 146 (51%) of queried centers and were stratified into five distinct geographic regions (North America, Central and South America, Oceana, Europe, and Asia). Most of the responding centers reported use of hard shell venous reservoirs. Closed venous systems were used at 50% of reporting centers in Central and South America as compared with only 3% in North America and 10% in Asia. Seventy-one percent of the programs used some form of modified ultrafiltration. Use of an arterial bubble detection system varied between 50% use (Central and South America) vs. 100% (North America and Oceana). "Del Nido" cardioplegia is more common in North America (32%) than any other continent, whereas Custodial HTK solution is much more prevalent in Europe (31%). Wide variation in practice was evident across geographic regions, suggesting opportunities for further investigation and improvement.

2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines.

BACKGROUND: Practice guidelines reflect published literature. Because of the ever changing literature base, it is necessary to update and revise guideline recommendations from time to time. The Society of Thoracic Surgeons recommends review and possible update of previously published guidelines at least every three years. This summary is an update of the blood conservation guideline published in 2007. METHODS: The search methods used in the current version differ compared to the previously published guideline. Literature searches were conducted using standardized MeSH terms from the National Library of Medicine PUBMED database list of search terms. The following terms comprised the standard baseline search terms for all topics and were connected with the logical 'OR' connector--Extracorporeal circulation (MeSH number E04.292), cardiovascular surgical procedures (MeSH number E04.100), and vascular diseases (MeSH number C14.907). Use of these broad search terms allowed specific topics to be added to the search with the logical 'AND' connector. RESULTS: In this 2011 guideline update, areas of major revision include: 1) management of dual anti-platelet therapy before operation, 2) use of drugs that augment red blood cell volume or limit blood loss, 3) use of blood derivatives including fresh frozen plasma, Factor XIII, leukoreduced red blood cells, platelet plasmapheresis, recombinant Factor VII, antithrombin III, and Factor IX concentrates, 4) changes in management of blood salvage, 5) use of minimally invasive procedures to limit perioperative bleeding and blood transfusion, 6) recommendations for blood conservation related to extracorporeal membrane oxygenation and cardiopulmonary perfusion, 7) use of topical hemostatic agents, and 8) new insights into the value of team interventions in blood management. CONCLUSIONS: Much has changed since the previously published 2007 STS blood management guidelines and this document contains new and revised recommendations.

Diagnosis of inadvertent cannulation of the azygos vein during cardiopulmonary bypass.

Cardiac surgery with cardiopulmonary bypass demands diligence and attention to detail to prevent neurologic injury. Arterial and venous cannulae are used to facilitate cardiopulmonary bypass. The assessment of adequate decompression of the venous circulation is an essential duty of the cardiac surgical team. Modalities for the assessment of adequate regional venous drainage are limited, however communication between the team and increased awareness of certain pathologic states can be useful. These modalities include cerebral oximetry and superior vena caval pressure monitoring, which were employed during a case with bicaval venous cannulation. Malposition of the superior vena cava cannula was detected after a series of events alerted the team that superior vena cava drainage may be compromised.

The effect of the perioperative blood transfusion and blood conservation in cardiac surgery Clinical Practice Guidelines of the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists upon clinical practices.

The 2007 Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Clinical Practice Guideline for Perioperative Blood Transfusion and Blood Conservation in Cardiac Surgery was recently promulgated and has received much attention. Using a survey of cardiac anesthesiologists and perfusionists' clinical practice, we assessed the current practices of perfusion, anesthesia, and surgery, as recommended by the Guidelines and also determined the role the Guidelines had in changing these practices. Nontrainee members of the Society of Cardiovascular Anesthesiologists, the American Academy of Cardiovascular Perfusion, the Canadian Society of Clinical Perfusion, and the American Society of ExtraCorporeal Technology were surveyed using a standardized survey instrument that examined clinical practices and responses to the Guidelines. One thousand four hundred and two surveys from 1,061 institutions principally in the United States (677 institutions) and Canada (34 institutions) were returned, with a 32% response rate. There was wide distribution of the Guidelines with 78% of anesthesiologists and 67% of perfusionists reporting having read all, part, or a summary of the Guidelines. However, only 20% of respondents reported that an institutional discussion had taken place as a result of the Guidelines, and only 14% of respondents reported that an institutional monitoring group had been formed. There was wide variability in current preoperative testing, perfusion, surgical, and pharmacological practices reported by respondents. Twenty-six percent of respondents reported one or more practice changes in response to the Guidelines.The changes made were reported to be highly (9%) or somewhat effective (31%) in reducing overall transfusion rates. Only four of 38 Guideline recommendations were reported by more than 5% of respondents to have been changed in response to the Guidelines. Wide variation in clinical practices of cardiac surgery was reported. Little change in clinical practices was attributed to the Society of Thoracic Surgeons/Society of Cardiovascular Anesthesiologists Guidelines.

Effect of the perioperative blood transfusion and blood conservation in cardiac surgery clinical practice guidelines of the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists upon clinical practices.

BACKGROUND: The 2007 Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Clinical Practice Guideline for Perioperative Blood Transfusion and Blood Conservation in Cardiac Surgery was recently promulgated and has received much attention. Using a survey of cardiac anesthesiologists and perfusionists' clinical practice, we aimed to assess the current practices of perfusion, anesthesia, and surgery, as recommended by the Guidelines, and to also determine the role the Guidelines had in changing these practices. METHODS: Nontrainee members of the Society of Cardiovascular Anesthesiologists, the American Academy of Cardiovascular Perfusion, the Canadian Society of Clinical Perfusion, and the American Society of ExtraCorporeal Technology were surveyed using a standardized survey instrument that examined clinical practices and responses to the Guidelines. RESULTS: A total of 1402 surveys from 1061 institutions principally in the United States (677 institutions) and Canada (34 institutions) were returned, a 32% response rate. There was wide distribution of the Guidelines with 78% of anesthesiologists and 67% of perfusionists reporting having read all, part, or a summary of the Guidelines. However, only 20% of respondents reported that an institutional discussion had taken place as a result of the Guidelines, and only 14% of respondents reported that an institutional monitoring group had been formed. There was wide variability in current preoperative testing, perfusion, surgical, and pharmacological practices reported by respondents. Twenty-six percent of respondents reported 1 or more practice changes in response to the Guidelines. The changes made were reported to be highly (9%) or somewhat (31%) effective in reducing overall transfusion rates. Only 4 of 38 Guideline recommendations were reported by >5% of respondents to have been changed in response to the Guidelines. CONCLUSIONS: Wide variation in clinical practices of cardiac surgery was reported. Little change in clinical practices was attributed to the Society of Thoracic Surgeons/Society of Cardiovascular Anesthesiologists Guidelines.