Lack of efficacy of aprotinin over tranexamic acid in type A aortic dissection repair.

BACKGROUND: The role of aprotinin in modern cardiac surgery is not well defined. While licensed for use in isolated coronary artery bypass grafting it is more commonly used for cases deemed to be at an increased risk of bleeding. The relative efficacy, and safety profile, of aprotinin as compared to other antifibrinolytics in these high-risk cases is uncertain. STUDY DESIGN AND METHODS: A retrospective observational study with propensity matching to determine whether aprotinin versus tranexamic acid reduced bleeding or transfusion requirements in patients presenting for surgical repair of type A aortic dissection (TAD). RESULTS: Between 2016 and 2022, 250 patients presented for repair of TAD. A total of 231 patients were included in the final analysis. Bleeding and transfusion were similar between both groups in both propensity matched and unmatched cohorts. Compared to tranexamic acid, aprotinin use did not reduce transfusion requirements for any product. Rates of bleeding in the first 12 h, return to theater and return to intensive care unit with an open packed chest were similar between groups. There was no difference in rates of renal failure, stroke, or death. CONCLUSION: Aprotinin did not reduce the risk of bleeding or transfusion requirements in patients undergoing repair of type A aortic dissections. Efficacy of aprotinin may vary depending on the type of surgery performed and the underlying pathology.

Assessing the impact of different heparin dosing regimens for cardiopulmonary bypass on anticoagulation: the HepDOSE pilot study.

PURPOSE: It has been suggested that a larger heparin dose during cardiopulmonary bypass (CPB) is associated with reduced perioperative coagulopathy and thromboembolic complications. We investigated the effect of different heparin doses during routine elective cardiac surgery. Our primary outcomes include blood loss and transfusion and secondary outcomes investigate the effects on coagulation biomarkers. METHODS: In this prospective pilot trial, we allocated 60 patients undergoing cardiac surgery on CPB in a single tertiary cardiac centre into three groups to receive an initial dose of 300, 400, or 500 units (U) per kilogram of intravenous heparin prior to the commencement of CPB. Blood was sampled after induction of anesthesia, at 30 and 60 min of CPB, and three minutes after heparin reversal with protamine. Samples were analyzed for fibrinopeptide A (FPA), fibrinopeptide B (FPB), D-dimer, and thrombin-antithrombin (TAT) complexes. Postoperative blood loss and transfusion was measured for the first 24-hr period after surgery. RESULTS: The total mean (95% CI) administered heparin dose in the 300 U·kg-1, 400 U·kg-1, and 500 U·kg-1 groups were 39,975 (36,528 to 43,421) U, 43,195 (36,940 to 49,449) U and 47,900 (44,807 to 50,992) U, respectively. There were no statistically significant differences in FPA, FPB or D-dimer levels at the measured time intervals. There was a trend towards lower TAT levels while on CPB with greater heparin dosing, which was statistically significant after the administration of protamine. The clinical significance appears to be negligible, as there is no difference in overall blood loss and amount of packed red blood cell transfusion or other blood product transfusion. CONCLUSION: This pilot study indicates that, while larger heparin dosing for routine cardiac surgery results in subtle biochemical changes in coagulation, there is no demonstrable benefit in postoperative blood loss or transfusion requirements.

RéSUMé: OBJECTIF: Il a été suggéré qu'une dose plus élevée d'héparine pendant la circulation extracorporelle (CEC) serait associée à une réduction de la coagulopathie périopératoire et des complications thromboemboliques. Nous avons étudié l'effet de différentes doses d'héparine au cours d'une chirurgie cardiaque non urgente de routine. Nos critères d'évaluation principaux comprenaient la perte de sang et la transfusion, et les critères d'évaluation secondaires exploraient les effets sur les biomarqueurs de la coagulation. MéTHODE: Dans cette étude pilote prospective, nous avons réparti 60 patient·es bénéficiant d'une chirurgie cardiaque sous CEC dans un seul centre cardiaque tertiaire en trois groupes à recevoir une dose initiale de 300, 400 ou 500 unités (U) par kilogramme d'héparine intraveineuse avant le début de la CEC. Le sang a été prélevé après l'induction de l'anesthésie, à 30 et 60 minutes de CEC, et trois minutes après la neutralisation de l'héparine avec la protamine. Les échantillons ont été analysés pour les complexes fibrinopeptide A (FPA), fibrinopeptide B (FPB), D-dimère et thrombine-antithrombine (TAT). La perte de sang postopératoire et la transfusion ont été mesurées pendant la première période de 24 heures après la chirurgie. RéSULTATS: La dose moyenne totale (IC 95 %) d'héparine administrée dans les 300 U·kg−1, 400 U·kg−1, et 500 U·kg−1 était de 39 975 (36 528 à 43 421) U, 43 195 (36 940 à 49 449) U et 47 900 (44 807 à 50 992) U, respectivement. Il n'y avait aucune différence statistiquement significative dans les taux de FPA, FPB ou D-dimères aux intervalles de temps mesurés. Une tendance à des niveaux de TAT plus bas pendant la CEC a été observée avec une dose d'héparine plus élevée, ce qui était statistiquement significatif après l'administration de protamine. La signification clinique semble négligeable, car il n'y a pas de différence dans la perte de sang globale et la quantité de transfusion de concentrés globulaires ou d'autres produits sanguins. CONCLUSION: Cette étude pilote indique que, bien qu'une dose plus importante d'héparine pour la chirurgie cardiaque de routine entraîne des changements biochimiques subtils dans la coagulation, il n'y a aucun avantage démontrable en matière de saignement postopératoire ou de besoins transfusionnels.

Association of Passive Lung Insufflation Oxygen Fraction in Adult Patients on Cardiopulmonary Bypass with Postoperative Pulmonary Outcomes: A Retrospective Cohort Study.

OBJECTIVES: To determine whether FIO2 of passive lung insufflation during cardiopulmonary bypass correlates with postoperative pulmonary function. DESIGN: A retrospective, observational study SETTING: A single-center, university-affiliated, specialist cardiothoracic center in the United Kingdom. PARTICIPANTS: Adult patients presenting for nonemergency, nontransplant cardiac surgery requiring cardiopulmonary bypass without the need for deep hypothermic circulatory arrest between January 1, 2018, and December 31, 2018. INTERVENTIONS: Passive insufflation of the lungs during cardiopulmonary bypass with fresh gas flow of varying FIO2. Patients were sorted retrospectively into low FIO2 (0.21-0.44), intermediate FIO2 (0.45-0.69), and high FIO2 (0.7-1.0) groups. The primary outcome was the difference between the PaO2:FIO2 on the first postinduction blood gas and on the first blood gas recorded postoperatively in the intensive care unit (ICU) (delta PaO2:FIO2). Secondary outcomes were ICU and hospital lengths of stay, requirement for respiratory support, and 30-day mortality. MEASUREMENTS AND MAIN RESULTS: Nine hundred patients were included in the authors' analysis (low FIO2 n = 307, intermediate FIO2 n = 459, high FIO2 n = 134). There was no significant difference in delta PaO2:FIO2 among the groups (low FIO2 = 52.5 [-38.8 to 152.4], intermediate FIO2 = 71.8 [-39.4 to 165.1], high FIO2 = 60.2 [-19.2 to 184.0], p = 0.25). There were no significant differences among groups for any secondary outcomes. CONCLUSION: Fresh gas flow with a low FIO2 delivered to the lungs without positive airway pressure during cardiopulmonary bypass was not associated with improved postoperative pulmonary function when compared to higher FIO2 levels.

Pulsatile Perfusion during Cardiopulmonary Bypass: A Literature Review.

The use of cardiopulmonary bypass (CPB) in cardiac surgery has often been associated with postoperative organ dysfunction. Roller and centrifugal pumps produce non-pulsatile flow (NPF) by default, and this still is the most widely used mode of perfusion. The development of pulsatile pumps has allowed comparisons to be made with NPF. Pulsatile flow (PF) mimics the arterial pulse generated by the heart and is thought to be more physiological by some. This review aims to examine the proposed mechanisms behind the potential physiological benefits of PF during CPB and to summarize the current clinical evidence. MEDLINE and EMBASE were used to identify articles published over a 25 year period from 1995 to 2020. A literature review was conducted to determine the effects of PF on organ functions. A total of 44 articles were considered. Most of the articles published on PF were randomized controlled trials (RCTs). However, there was a wide variation in study methodology, method of pulse generation and how pulsatility was measured. Most of the evidence in favor of PF showed a marginal improvement on renal and pulmonary outcomes. In these studies, pulsatility was generated by an intra-aortic balloon pump. In conclusion, there is a lack of good quality RCTs that can inform on the short- and long-term clinical outcomes of PF. Further research is required in order to draw a conclusion with regards to the benefits of PF on organ function.

Optimal protamine dosing after cardiopulmonary bypass: The PRODOSE adaptive randomised controlled trial.

BACKGROUND: The dose of protamine required following cardiopulmonary bypass (CPB) is often determined by the dose of heparin required pre-CPB, expressed as a fixed ratio. Dosing based on mathematical models of heparin clearance is postulated to improve protamine dosing precision and coagulation. We hypothesised that protamine dosing based on a 2-compartment model would improve thromboelastography (TEG) parameters and reduce the dose of protamine administered, relative to a fixed ratio. METHODS AND FINDINGS: We undertook a 2-stage, adaptive randomised controlled trial, allocating 228 participants to receive protamine dosed according to a mathematical model of heparin clearance or a fixed ratio of 1 mg of protamine for every 100 IU of heparin required to establish anticoagulation pre-CPB. A planned, blinded interim analysis was undertaken after the recruitment of 50% of the study cohort. Following this, the randomisation ratio was adapted from 1:1 to 1:1.33 to increase recruitment to the superior arm while maintaining study power. At the conclusion of trial recruitment, we had randomised 121 patients to the intervention arm and 107 patients to the control arm. The primary endpoint was kaolin TEG r-time measured 3 minutes after protamine administration at the end of CPB. Secondary endpoints included ratio of kaolin TEG r-time pre-CPB to the same metric following protamine administration, requirement for allogeneic red cell transfusion, intercostal catheter drainage at 4 hours postoperatively, and the requirement for reoperation due to bleeding. The trial was listed on a clinical trial registry (ClinicalTrials.gov Identifier: NCT03532594). Participants were recruited between April 2018 and August 2019. Those in the intervention/model group had a shorter mean kaolin r-time (6.58 [SD 2.50] vs. 8.08 [SD 3.98] minutes; p = 0.0016) post-CPB. The post-protamine thromboelastogram of the model group was closer to pre-CPB parameters (median pre-CPB to post-protamine kaolin r-time ratio 0.96 [IQR 0.78-1.14] vs. 0.75 [IQR 0.57-0.99]; p < 0.001). We found no evidence of a difference in median mediastinal/pleural drainage at 4 hours postoperatively (140 [IQR 75-245] vs. 135 [IQR 94-222] mL; p = 0.85) or requirement (as a binary outcome) for packed red blood cell transfusion at 24 hours postoperatively (19 [15.8%] vs. 14 [13.1%] p = 0.69). Those in the model group had a lower median protamine dose (180 [IQR 160-210] vs. 280 [IQR 250-300] mg; p < 0.001). Important limitations of this study include an unblinded design and lack of generalisability to certain populations deliberately excluded from the study (specifically children, patients with a total body weight >120 kg, and patients requiring therapeutic hypothermia to <28°C). CONCLUSIONS: Using a mathematical model to guide protamine dosing in patients following CPB improved TEG r-time and reduced the dose administered relative to a fixed ratio. No differences were detected in postoperative mediastinal/pleural drainage or red blood cell transfusion requirement in our cohort of low-risk patients. TRIAL REGISTRATION: ClinicalTrials.gov Unique identifier NCT03532594.

Thrombotic risk in central venoarterial extracorporeal membrane oxygenation post cardiac surgery.

INTRODUCTION: Post-cardiotomy cardiogenic shock is an accepted indication for venoarterial extracorporeal membrane oxygenation. The true incidence and risk factors for the development of thrombosis in this setting remain unclear. METHODS: Patients supported with central venoarterial extracorporeal membrane oxygenation due to ventricular dysfunction precluding weaning from cardiopulmonary bypass were retrospectively identified. Electronic records from a single institution spanning a 4-year period from January 2015 to December 2018 were interrogated to assess the incidence of thrombosis. The relationship to exposures including intracardiac stasis and procoagulant usage was explored. RESULTS: Twenty-four patients met the inclusion criteria and six suffered major intracardiac thrombosis. All cases of thrombosis occurred early, and none survived to hospital discharge. The lack of left ventricular ejection conferred a 46% risk of developing thrombosis compared to 0% if ejection was maintained (p = 0.0093). Aprotinin use was also associated with thrombus formation (p = 0.035). There were no significant differences between numbers of patients receiving other procoagulants when grouped by thrombosis versus no thrombosis. CONCLUSION: Stasis is the predominant risk factor for intracardiac thrombosis. This occurs rapidly and the outcome is poor. As a result, we suggest early left ventricular decompression. Conventional management of post-bypass coagulopathy seems safe if the aortic valve is opening.

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.

Evaluation of Increase in Intraoperative Lactate Level as a Predictor of Outcome in Adults After Cardiac Surgery.

OBJECTIVES: Early onset hyperlactatemia develops intraoperatively or within the first 6 hours of admission to the intensive care unit (ICU) and is associated with a poor prognosis. The aim of the present study was to determine the utility of an increase in the intraoperative lactate level, independent of the absolute lactate value at baseline after induction, as a dynamic parameter for morbidity (ICU length of stay, postoperative renal failure, and inotrope use) and mortality in adults post-cardiac surgery. DESIGN: Retrospective observational study. SETTING: Single-center study in an academic hospital. PARTICIPANTS: The study comprised 779 patients who underwent elective cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were classified into the following 5 groups based on the increase in the intraoperative lactate level: (1) group 1-negative, (2) group 2-1- to 1.59-fold increase, (3) group 3-1.6- to 1.99-fold increase, (4) group 4-2- to 3-fold increase, and (5) group 5->3-fold increase. Logistic regression analyses were performed. Group 5 had a 4 times greater mortality (7.7%), the longest ICU length of stay (89.02 ± 78.73 h), and the greatest incidence of postoperative renal failure (n = 5 [19.2%]) compared with group 1. The increase in the intraoperative lactate level was a statistically significant predictor of mortality (p = 0.001) and ICU length of hospital stay (p = 0.0006) and was highly predictive for postoperative renal failure requiring renal replacement therapy (p = 0.001). CONCLUSIONS: An increase in intraoperative lactate, independent of the level on induction, is a useful dynamic parameter to identify patients at risk of postoperative morbidity and mortality and might provide an early trigger for introducing measures to avoid poor outcomes.

The Association Between Pulsatile Cardiopulmonary Bypass and Acute Kidney Injury After Cardiac Surgery: A Before-and-After Study.

OBJECTIVES: To investigate the association between pulsatile perfusion and cardiac surgery-associated acute kidney injury. DESIGN: An uncontrolled, retrospective before-and-after study. SETTING: Single tertiary hospital. PARTICIPANTS: A total of 2,489 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: Pulsatile versus nonpulsatile perfusion. MEASUREMENTS AND MAIN RESULTS: Data for nonpulsatile perfusion was collected from April 1, 2016, to March 31, 2017 (n = 1,223). A practice change to universal pulsatile CPB occurred on April 3, 2017. Data for pulsatile perfusion was collected from May 1, 2017, to June 30, 2018 (n = 1,266). The primary outcome was the incidence of acute kidney injury (AKI) after cardiac surgery. Multivariable analysis was carried out to adjust for known confounders. Secondary outcomes included AKI stage, stroke, length of stay, and mortality. Subgroup analyses were carried out using prolonged CPB and chronic kidney disease. The primary outcome, incidence of AKI, did not differ between the nonpulsatile control group and the pulsatile group (23.9% v 25.4%, p = 0.392). The pulsatile group was not associated with AKI in the multivariable analysis (Odds ratio 1.09, p = 0.413). There were no differences in stages of AKI in the nonpulsatile group v pulsatile group (13.6% v 14.9%, 2.9% v 4.3%, and 7.4% v 6.1% for stages 1, 2, and 3, respectively, p = 0.12). There were no differences in subgroup analyses or secondary outcomes. CONCLUSIONS: There was no association found between kidney injury and pulsatile perfusion. It is likely that there is either no association between pulsatile perfusion and reduced kidney injury or that the difference is extremely small.

Are We Able to Dose Protamine Accurately Yet? A Review of the Protamine Conundrum.

Without anticoagulation, cardiopulmonary bypass would not have developed over the last nearly 60 years into one of the most influential innovations in medicine; without the ability to reverse anticoagulation, cardiac surgery might not have become the common intervention, which is now practiced globally. Despite the recent breathtaking developments in extracorporeal technology, heparin and protamine remain the pillars of anticoagulation and its reversal until this day. However, there is still much controversy in particular about protamine dosing regimens. A number of recent publications investigating various approaches to dosing protamine have rekindled this debate. This review is seeking to capture the current thinking about protamine dosing after cessation of cardiopulmonary bypass.

Circulatory support during lung transplantation.

PURPOSE OF REVIEW: Lung transplantation can be performed off-pump, with sequential one-lung ventilation, or using mechanical circulatory support (MCS). MCS can either be in the form of cardiopulmonary bypass (CPB) or veno-arterial or veno-venous extracorporeal membrane oxygenation (VA ECMO or VV ECMO).This article reviews the indications, benefits and limitations of these different techniques and evaluates their effect on outcomes. RECENT FINDINGS: Recently, there has been a shift toward intraoperative ECMO support and away from CPB. The first results of this strategy are promising. The use of intraoperative ECMO with the possibility of prolongation of MCS into the postoperative period has been shown to lead to improved survival when compared with lung transplants not receiving ECMO. Recipients of organs from extended criteria donors show encouraging survival rates when the lungs are reperfused using MCS. A recent metaanalysis comparing ECMO versus CPB showed favourable outcomes supporting the use of ECMO despite not finding a difference in mortality between the two methods. SUMMARY: The trend toward ECMO and away from cardiopulmonary bypass is backed up with good survival rates. However, to date, there has not been a randomized controlled trial to further guide the choice of MCS strategy for lung transplantation.

New Strategies to Expand and Optimize Heart Donor Pool: Ex Vivo Heart Perfusion and Donation After Circulatory Death: A Review of Current Research and Future Trends.

Heart transplantation remains the definitive management for end-stage heart failure refractory to medical therapy. While heart transplantation cases are increasing annually worldwide, there remains a deficiency in organ availability with significant patient mortality while on the waiting list. Attempts have therefore been made to expand the donor pool and improve access to available organs by recruiting donors who may not satisfy the standard criteria for organ donation because of donor pathology, anticipated organ ischemic time, or donation after circulatory death. "Ex vivo" heart perfusion (EVHP) is an emerging technique for the procurement of heart allografts. This technique provides mechanically supported warm circulation to a beating heart once removed from the donor and before implantation into the recipient. EVHP can be sustained for several hours, facilitate extended travel time, and enable administration of pharmacological agents to optimize cardiac recovery and function, as well as allow assessment of allograft function before implantation. In this article, we review recent advances in expanding the donor pool for cardiac transplantation. Current limitations of conventional donor criteria are outlined, including the determinants of organ suitability and assessment, involving transplantation of donation after circulatory death hearts, extended criteria donors, and EVHP-associated assessment, optimization, and transportation. Finally, ongoing research relating to organ optimization and functional ex vivo allograft assessment are reviewed.

Three consecutive cases of fatal intraoperative intracardiac thrombosis associated with the initiation of venoarterial extracorporeal membrane oxygenation in the presence of aprotinin.

Central venoarterial extracorporeal membrane oxygenation has been used since the 1970s to support patients with cardiogenic shock following cardiac surgery. Despite this, in-hospital mortality is still high, and although rare, thrombus within the cardiac chambers or within the extracorporeal membrane oxygenation circuit is often fatal. Aprotinin is an antifibrinolytic available in Europe and Canada, though not currently in the United States. Due to historical safety concerns, use of aprotinin is generally limited and is commonly reserved for patients with the highest bleeding risk. Given the limited availability of aprotinin over the last decade, it is not surprising to find a complete absence of literature describing the use of venoarterial extracorporeal membrane oxygenation in the presence of aprotinin. We present three consecutive cases of rapid fatal intraoperative intracardiac thrombosis associated with post-cardiotomy central venoarterial extracorporeal membrane oxygenation in patients receiving aprotinin.

Clinical Evaluation of Measuring the ACT during Elective Cardiac Surgery with Two Different Devices.

Unfractionated heparin is the mainstay of anticoagulation during cardiac surgery on cardiopulmonary bypass (CPB) due to its low cost, quick onset, and ease of reversal. Since over 30 years, the activated clotting time (ACT) has been used to assess the level of heparin activity both before and after CPB. We compared two different methods of measuring the ACT: i-STAT, which uses amperometric detection of thrombin cleavage, and Hemochron Jr, which is based on detecting viscoelastic changes in blood. We included 402 patients from three institutions (Papworth Hospital, Cambridge, UK; Groote Schuur, Cape Town, South Africa; University Hospital Basel, Basel, Switzerland) undergoing elective cardiac surgery on CPB in our study. We analyzed duplicate samples on both devices at all standard measuring points during the procedure. The correlation coefficient between two Hemochron and two i-STAT devices was .9165 and .9857, respectively. The within-subject coefficient of variation (WSCV) ranged from 8.2 to 13.6% for the Hemochron and from 4.1 to 9.1% for the i-STAT. We found that the number of occasions where one of the duplicate readings was >1,000 seconds while the other was below or close to the clinically significant threshold of 400 seconds were higher for the Hemochron. We found the i-STAT to systematically return higher measurements. We conclude that the i-STAT provides a more reliable test for heparin activity and assesses safe anticoagulation during cardiac surgery on pump. The fact the that the i-STAT reads higher than the Hemochron leads to the recommendation to validate the methods against each other before changing devices.

Global Cardioplegia Practices: Results from the Global Cardiopulmonary Bypass Survey.

Despite the ubiquitous use of cardioplegia in cardiac surgery, there is a lack of agreement on various aspects of cardioplegia practice. To discover current cardioplegia practices throughout the world, we undertook a global survey to document contemporary cardiopulmonary bypass practices. A 16-question, Internet-based survey was distributed by regional specialist societies, targeting adult cardiac anesthesiologists. Ten questions concerned caseload and cardioplegia practices, the remaining questions examined anticoagulation and pump-priming practices. The survey was available in English, Spanish, and Portuguese. The survey was launched in June 2015 and remained open until May 2016. A total of 923 responses were analyzed, summarizing practice in Europe (269), North America (334), South America (215), and Australia/New Zealand (105). Inter-regional responses differed for all questions asked (p < .001). In all regions other than South America, blood cardioplegia was the common arrest technique used. The most commonly used cardioplegia solutions were: St. Thomas, Bretschneider, and University of Wisconsin with significant regional variation. The use of additives (most commonly glucose, glutamate, tris-hydroxymethyl aminomethane, and aspartate) varied significantly. This survey has revealed significant variation in international practice with regards to myocardial protection, and is a reminder that there is no clear consensus on the use of cardioplegia. It is unclear why regional practice groups made the choices they have and the clinical impact remains unclear.

Pump Priming Practices and Anticoagulation in Cardiac Surgery: Results From the Global Cardiopulmonary Bypass Survey.

BACKGROUND: Regional patterns of practice in cardiopulmonary bypass remain poorly understood with conflicting evidence regarding the best choices in pump priming preferences with respect to colloid and crystalloid and different types of fluid within these categories. In light of the variation in the literature, we hypothesized there would be considerable regional differences in cardiopulmonary bypass practice, particularly with respect to the type of fluid used to prime the extracorporeal circuit. METHODS: A 16-question, Internet-based survey was distributed by various regional specialist societies, targeting adult cardiac anesthesiologists. One question was directly relevant to activated clotting time and 5 concerned pump priming choices with respect to crystalloid and colloid types and additives. The remaining questions concerned cardioplegia choices. The survey remained open from June 2015 to May 2016. RESULTS: A total of 923 responses were analyzed. Estimated response rates from Europe, North America, Australia/New Zealand, and South America were 19.77%, 8.06%, 16.30%, and 1.68%, respectively. The majority of respondents worldwide considered an activated clotting time of <400 seconds as unsafe for bypass (92.5%). Crystalloid as a sole fluid type remains the most common priming solution worldwide (38.1%) although combinations with colloid (23.8%) were also popular. Retrograde autologous priming was used by 17.9% of respondents. Heparin was the most frequently used prime additive (43.0%) followed by mannitol (35.2%). Variation was demonstrated within some of these categories reflective of differences in regional practices. CONCLUSIONS: Differences exist in some specific areas between regional cardiopulmonary bypass techniques with respect to pump priming and anticoagulation practices. The significance of these differences with respect to patient outcome is uncertain and requires further study.

Pilot validation of an individualised pharmacokinetic algorithm for protamine dosing after systemic heparinisation for cardiopulmonary bypass.

INTRODUCTION: This manuscript represents a pilot study assessing the feasibility of a single-compartment, individualised, pharmacokinetic algorithm for protamine dosing after cardiopulmonary bypass. METHODS: A pilot cohort study in a specialist NHS cardiothoracic hospital targeting patients undergoing elective cardiac surgery using cardiopulmonary bypass. Patients received protamine doses according to a pharmacokinetic algorithm (n = 30) or using an empirical, fixed-dose model (n = 30). Categorical differences between the groups were evaluated using the Chi-squared test or Fisher's exact test. Continuous data was analysed using a paired Student's t-test for parametric data and the paired samples Wilcoxon test for non-parametric data. RESULTS: Patients who had protamine dosing according to the algorithm demonstrated a lower protamine requirement post-bypass relative to empirical management as measured by absolute dose (243 ± 49mg vs. 305 ± 34.7mg; p<0.001) and the heparin to protamine ratio (0.79 ± 0.12 vs. 1.1 ± 0.15; p<0.001). There was no difference in the pre- to post-bypass activated clotting time (ACT) ratio (1.05 ± 0.12 vs. 1.02 ± 0.15; p=0.9). Patients who received protamine according to the algorithm had no significant difference in transfusion requirement (13.3% vs. 30.0%; p=0.21). CONCLUSIONS: This study showed that an individualized pharmacokinetic algorithm for the reversal of heparin after cardiopulmonary bypass is feasible in comparison with a fixed dosing strategy and may reduce the protamine requirement following on-pump cardiac surgery.