Protamine Administration Research Articles

The hemodynamic effects of protamine in pediatric patients undergoing pulmonary artery reconstruction and unifocalization surgery: A Pilot Study.: Hemodynamic effects of protamine in children.

ObjectivesTo determine protamine administration increases pulmonary artery pressures in patients undergoing unifocalization or pulmonary artery reconstruction surgeries. Design: Retrospective database study. SettingA large pediatric heart center within an academic quaternary care facility. ParticipantsAll patients undergoing pulmonary artery reconstruction or unifocalization procedure identifiable within the data warehouse. InterventionsWe collected data from Stanford University's data repository, formatted it, and analyzed it using RStudio (v 2023.06.1+524). Measurements and Main ResultsOur primary outcome is the change in pulmonary artery pressure (PAP) after an administration of protamine. Secondary outcomes include changes in the mean arterial pressure, the ratio of systolic pulmonary artery to systemic artery pressure, right sided filling pressure, and left atrial pressure. After a protamine bolus, we found a difference in PAP (Friedman X2 = 49.46, p <0.001). When compared to two minutes before its administration, the PAP was higher at two minutes (29.00 mmHg versus 25.00 mmHg, p <0.001), five minutes (30.00 mmHg versus 25.00 mmHg, p <0.001) and ten minutes (31 mmHg versus 25 mmHg, p < 0.001). When co-administered with calcium, there was also a significant increase in PAP (Friedman X2 = 28.11, p < 0.001), with a higher PAP ten minutes after calcium administration when compared to two minutes before (32 mmHg versus 26 mmHg, p < 0.001) Conclusions: Protamine administration led to a small increase in PAP after separation from cardiopulmonary bypass in patients undergoing pulmonary artery reconstruction or unifocalization surgeries. Calcium co-administration did not lead to a greater increase in PAP.

Protamine administration after catheter ablation of atrial fibrillation using electroporation: a randomized controlled trial

Abstract Background Safety of protamine administration after catheter ablation of atrial fibrillation (AF) using pulse-field system has not been previously described in a prospective randomized trial. Methods Consecutive patients with paroxysmal, persistent or long-standing persistent AF undergoing catheter ablation of AF using Farapulse system were randomly assigned in 1:1 ratio for protamine administration before sheaths removal. All vascular punctions were navigated using a direct ultrasound control. Right femoral vein was used for FaraDrive (16 F) sheath and left femoral vein for ICE (11 F) and decapolar diagnostic catheter (7 F). All sheaths were removed immediately at the end of procedure with subsequent local haemostasis with figure-of-eight suture. Primary endpoint was early and late access site complications. Secondary endpoints were significant bleeding, thromboembolic events and duration of hospital stay. Results 428 consecutive patients were enlisted into the study (213 in protamine group; 215 in control group). Baseline and procedural characteristics were similar between both groups. ACT before venous sheath removal was higher in patients not receiving protamine (330.1 ± 38.6 vs. 189.3 ± 44.7 seconds, P &amp;lt; 0.001). There were no significant differences in both primary and secondary endpoints between both groups: groin hematoma (5 vs 5; p = NS); there were no thromboembolic complications in both groups and no significant differences of hospital stay duration. Conclusion Protamine administration after atrial fibrillation ablation using Farapulse system is not necessary when using ultrasound navigated vascular access and haemostasis with figure of eight suture.

Protamine Dosing for Heparin Reversal Following Cardiopulmonary Bypass: A Double-Blinded Prospective Randomized Control Trial Comparing Two Strategies.

Drug shortages are a frequent challenge in current clinical practice. Certain drugs, (e.g., protamine) lack alternatives and inadequate supplies can limit access to services. Conventional protamine dosing uses heparin ratio-based calculations for heparin reversal following CPB and may result in excess protamine utilization, and potential harm due to its intrinsic anticoagulation. We hypothesized that a fixed 250-mg protamine dose would be comparable, as measured by the activated clotting time, to a 1:1 (1 mg for every 100 U) protamine to heparin ratio-based strategy for heparin reversal and that protamine would be conserved. In a single-center, double-blinded trial, consenting elective adult cardiac surgical patients without pre-existing coagulopathy or ongoing anticoagulation, and a calculated initial heparin dose of ≥ 27500 U were randomized to receive, following CPB, protamine as a fixed dose (250 mg) or a ratio-based dose (1 mg:100 U heparin). The primary outcome was the activated clotting time following initial protamine administration, assessed by Student's t-test. Secondary outcomes included total protamine, the need for additional protamine, and the cumulative 24-h chest tube output. There were 62 and 63 patients in the fixed- and ratio-based dose groups, respectively. The mean post-protamine ACT was not different between groups (-2.0 s, 95% CI -7.2 to 3.3 s, P = 0.47). Less total protamine per case was administered in the fixed-dose group (2.1 50-mg vials, 95% CI -2.4 to -1.8, P < 0.0001). There was no difference in the cumulative 24-h chest tube output (difference = -77 ml, 95% CI 220 to 65 ml, P = 0.28). A 1: 1 heparin ratio-based protamine dosing strategy compared to a fixed 250-mg dose resulted in the administration of a larger total dose of protamine no difference in either the initial ACT or the amount postoperative chest-tube bleeding.

A Randomized Controlled Trial Comparing Effectiveness of Different Fibrinogen Preparations in Restoring Clot Firmness.

Different preparations of fibrinogen concentrate are currently available. Two in vitro studies demonstrated the superiority of FibCLOT (LFB) in increasing clot firmness with respect to RiaSTAP (CSL Behring). The present trial involved a clinical model to test the hypothesis of superiority, with the increase in clot firmness as the primary end point. Forty cardiac surgery patients were randomly allocated to receive a dose of 30 mg/kg FibCLOT or RiaSTAP after protamine administration in the presence of microvascular bleeding and a FIBTEM maximum clot firmness (MCF) <10 mm. Viscoelastic parameters were measured before and after fibrinogen supplementation: FIBTEM MCF, EXTEM MCF, and EXTEM clotting time (CT). The mean increase in FIBTEM MCF was 4 ± 1.2 mm (mean and standard deviation) in the FibCLOT group and 4 ± 1.6 mm in the RiaSTAP group (P = 1.000); the mean decrease in CT was 11. 2 ± 12.2 (mean and standard deviation) seconds in the FibCLOT group and 14. 8 ± 13 seconds in the RiaSTAP group (P = .372). In both groups, fibrinogen supplementation induced a significant (P = .001) increase in the FIBTEM MCF and EXTEM CT. The proportions of patients who did not experience an increase of 4 mm in the RiaSTAP group and the FibCLOT group were not statistically significantly higher (35% vs 20%, respectively, relative risk 2.15, 95% confidence interval 0.52-9.00, P = .288). In contrast to previous in vitro studies, we found that the effect of FibCLOT on MCF and CT was not significantly greater than that of RiaSTAP in cardiac surgery patients. Further studies in other clinical settings are warranted.

Routine Protamine Administration for Bleeding in Transcatheter Aortic Valve Implantation

Vascular complications after transfemoral transcatheter aortic valve implantation (TAVI) remain an important cause of procedure-related morbidity. Routine reversal of anticoagulation with protamine at the conclusion of transfemoral TAVI could reduce complications, but data remain scarce. To evaluate the efficacy and safety of routine protamine administration after transfemoral TAVI. The ACE-PROTAVI trial was an investigator-initiated, double-blind, placebo-controlled randomized clinical trial performed at 3 Australian hospitals between December 2021 and June 2023 with a 1-year follow-up period. All patients accepted for transfemoral TAVI by a multidisciplinary heart team were eligible for enrollment. Eligible patients were randomized 1:1 between routine protamine administration and placebo. The coprimary outcomes were the rate of hemostasis success and time to hemostasis (TTH), presented as categorical variables and compared with a χ2 test or as continuous variables as mean (SD) or median (IQR), depending on distribution. The major secondary outcome was a composite of all-cause death, major and minor bleeding complications, and major and minor vascular complications after 30 days, reported in odds ratios (ORs) with 95% CIs and P values. The study population consisted of 410 patients: 199 patients in the protamine group and 211 in the placebo group. The median (IQR) patient age in the protamine group was 82 (77-85) years, and 68 of 199 patients receiving protamine (34.2%) were female. The median (IQR) patient age in the placebo group was 80 (75-85) years, and 89 of 211 patients receiving the placebo (42.2%) were female. Patients receiving up-front protamine administration had a higher rate of hemostasis success (188 of 192 patients [97.9%]) than patients in the placebo group (186 of 203 patients [91.6%]; absolute risk difference, 6.3%; 95% CI, 2.0%-10.6%; P = .006); in addition, patients receiving up-front protamine had a shorter median (IQR) TTH (181 [120-420] seconds vs 279 [122-600] seconds; P = .002). Routine protamine administration resulted in a reduced risk of the composite outcome in the protamine group (10 of 192 [5.2%]) vs the placebo group (26 of 203 [12.8%]; OR, 0.37; 95% CI, 0.1-0.8; P = .01). This difference was predominantly driven by the difference in the prevalence of minor vascular complications. There were no adverse events associated with protamine use. In the ACE-PROTAVI randomized clinical trial, routine administration of protamine increased the rate of hemostasis success and decreased TTH. The beneficial effect of protamine was reflected in a reduction in minor vascular complications, procedural time, and postprocedural hospital stay duration in patients receiving routine protamine compared with patients receiving placebo. anzctr.org.au Identifier: ACTRN12621001261808.

Assessment of Perioperative Protamine Reactions in Patients With Fish Allergies: A Retrospective Observational Study

ObjectivesThis study retrospectively assessed the incidence and severity of perioperative protamine reactions in adult patients with documented history of fish allergy. DesignRetrospective, observational. SettingLarge, academic tertiary referral center. ParticipantsAdults with fish allergies undergoing surgeries involving protamine, from January 1, 2008, to March 1, 2018. InterventionsPerioperative protamine administration in patients with documented fish allergy. Measurements and Main ResultsWe reviewed perioperative protamine and anaphylactic reactions. A diagnosis of anaphylaxis or protamine reaction was based on clinical suspicion, perioperative events, and postoperative evaluations. Among 214 patients, two cases (<1%) of anaphylaxis or protamine reactions occurred. Cardiac procedures were most common (67%). Median intraoperative heparin dosage was 46,000 IU, and protamine dosage was 310 mg. Nearly all patients (99%) were admitted to the ICU postoperatively, with a median hospital stay of 6.5 days [5.2, 14.6]. There were three deaths (1%) within 30 days and 15 (7%) within a year. ConclusionsOur study suggests that in patients with history of fish allergy, cross-reactivity with protamine is unlikely, as anaphylaxis and/or protamine reactions were rare among this patient population in the perioperative environment. Based on the findings herein, this study does not recommend avoiding protamine solely based on a history of fish allergy when heparin reversal is required during surgery.

In vitro protamine addition for coagulation assessment using TEG 6s system during cardiopulmonary bypass: a pilot study.

Systemic heparinization during cardiopulmonary bypass (CPB) can significantly affect thromboelastography (TEG). This study investigated the feasibility of adding protamine in vitroto allow assessment of coagulation status using the TEG 6s system during CPB. In this prospective observational study, 21 patients undergoing elective cardiac valve surgery were evaluated. During CPB, protamine was added in vitro to the heparinized blood of these patients at a concentration of 0.05mg/mL and analyzed with the TEG 6s (Pre). The TEG parameters were compared to those analyzed after CPB withdrawal and systemic protamine administration (Post). The citrated kaolin maximal amplitude (CK-MA) and the citrated functional fibrinogen maximal amplitude (CFF-MA) exhibited strong correlations between Pre and Post measurements (r = 0.790 and 0.974, respectively, P < 0.001 for both), despite significant mean differences (-2.23mm for CK-MA and -0.68mm for CFF-MA). Bland-Altman analysis showed a clinically acceptable agreement between Pre and Post measurement of CK-MA and CFF-MA (the percentage error was 10.6% and 12.2%, respectively). In contrast, the citrated kaolin reaction time (CK-R) showed no significant correlation between Pre and Post measurements (r = 0.328, P = 0.146), with a mean difference of 1.42min (95% CI: -0.45 to 3.29). In vitro protamine addition allows assessment of coagulation status during CPB using the TEG 6s system. CK-MA and CFF-MA measured during CPB using this method revealed a strong correlation and agreement with post-CPB measurements, suggesting that our method potentially facilitates early prediction of post-CPB coagulation status and decision-making on transfusion strategies. The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR, registration number: UMIN000041097, date of registration: July 13, 2020, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046925 ) before the recruitment of participants.

Effects of Fibrinogen Concentrate Supplementation on Postoperative Bleeding in Infants Undergoing Complex Cardiac Surgery.

The use of allogeneic blood products to restore hemostasis during pediatric cardiac surgery is associated with major risks. Consequently, there has been a growing interest in new patient blood management strategies, such as those based on the use of fibrinogen concentrate (FC). Accumulating evidence has shown FC supplementation to be safe and effective. Nevertheless, no guidelines are available on using FC in the pediatric setting, and few objective evaluations have been provided in clinical practice. The endpoint of this monocenterretrospective study was the hemostatic effect of additional FC in infants undergoing complex cardiac surgery with cardiopulmonary bypassto manage persistent clinically relevant bleeding. After weaning from cardiopulmonary bypass and after protamine administration, patients were transfused with conventional allogeneic products such as packed red blood cells, fresh frozen plasma (FFP), and platelets. In the case of redo surgery, according to the institutional protocol, patients also received tranexamic acid. In case of clinically persistent relevant bleeding, according to the anesthesiologist's judgment and thromboelastography, patients received FC supplementation (group with FC) or further FFP transfusions without receiving FC supplementation (group without FC). The primary endpoint was the hemostatic effects of FC. Secondary endpoints were the functional hypofibrinogenemia threshold value (expressed as maximum amplitude fibrinogen, MA-Fib) and postoperative MA-Fib, fibrinogenemia, intraoperative transfusions, and adverse events (AEs). In total, 139 patients who underwent cardiac surgery with CPB and aged less than 2 years were enrolled: 70 patients received allogeneic blood products and FC supplementation (group FC); 69 patients received allogeneic products without FC supplementation (group without FC). Patients that received FC supplementation were characterized by a significantly longer time of extracorporeal circulation (p < 0.001) and aortic cross-clamping (p < 0.001), a significantly lower minimum temperature (p = 0.011), increased use of concentrated prothrombin complex (p = 0.016) and tranexamic acid (p = 0.010), and a significantly higher amount of packed red blood cells, platelets (p < 0.001) and fresh frozen plasma (p = 0.03). Postoperative bleeding and severe bleeding were not statistically different between patients treated with FC and those not treated with FC supplementation (p = 0.786 and p = 0.695, respectively); after adjustment, a trend toward reduced bleeding can be observed with FC (p = 0.064). Overall, 88% of patients with severe bleeding had MA-Fib < 10 mm; a moderate association between severe bleeding and MA-Fib (odds ratio 1.7, 95% CI 0.5-6.5, p = 0.425) was found. Increased MA-Fib and postoperative fibrinogen were higher in the FC group (p = 0.003 and p < 0.001, respectively) than in FFP. AEs in the FC group were comparable to those observed in less complicated surgeries. Our results suggest a potential role of FC in complex surgery in maintaining postoperative bleeding at a level comparable to less complicated surgical procedures and favoring the increase in postoperative MA-Fib and fibrinogen.

Perfusion Measures and Outcomes (PERForm) registry: First annual report.

The Perfusion Measures and Outcomes (PERForm) registry was established in 2010 to advance cardiopulmonary bypass (CPB) practices and outcomes. The registry is maintained through the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative and is the official registry of the American Society of Extracorporeal Technology. This first annual PERForm registry report summarizes patient characteristics as well as CPB-related practice patterns in adult (≥18 years of age) patients between 2019 and 2022 from 42 participating hospitals. Data from PERForm are probabilistically matched to institutional surgical registry data. Trends in myocardial protection, glucose, anticoagulation, temperature, anemia (hematocrit), and fluid management are summarized. Additionally, trends in equipment (hardware/disposables) utilization and employed patient safety practices are reported. A total of 40,777 adult patients undergoing CPB were matched to institutional surgical registry data from 42 hospitals. Among these patients, 54.9% underwent a CABG procedure, 71.6% were male, and the median (IQR) age was 66.0 [58.0, 73.0] years. Overall, 33.1% of the CPB procedures utilized a roller pump for the arterial pump device, and a perfusion checklist was employed 99.6% of the time. The use of conventional ultrafiltration decreased over the study period (2019 vs. 2022; 27.1% vs. 24.9%) while the median (IQR) last hematocrit on CPB has remained stable [27.0 (24.0, 30.0) vs. 27.0 (24.0, 30.0)]. Pump sucker termination before protamine administration increased over the study period: (54.8% vs. 75.9%). Few robust clinical registries exist to collect data regarding the practice of CPB. Although data submitted to the PERForm registry demonstrate overall compliance with published perfusion evidence-based guidelines, noted opportunities to advance patient safety and outcomes remain.

Ultrasound-guided venipuncture of femoral veins vs standard palpation approach in patients undergoing pulmonary veins isolation

Abstract Introduction Complications related to vascular access frequently arise during transcatheter atrial fibrillation (AF) ablation. Vascular access related complications remain the main cause of procedure related adverse events. In the literature, there is no clear evidence supporting the benefit of ultrasound-guided (USG) vascular access. Purpose We hypothesized that USG venipuncture could reduce vascular complication rates and reduce the need for additional interventions due to complications related to vascular access. Methods We conducted a single-center retrospective study. The primary endpoint was the rate of major complications, defined as arteriovenous fistula, pseudoaneurysm, and groin hematoma with Bleeding Academic Research Consortium (BARC) classification ≥ 2 requiring interventions such as transfusions or surgical/percutaneous repair and/or resulting in hospital prolongation or readmission). The secondary endpoints were the rate of minor complications, defined as groin hematoma with BARC classification = 1 or bleeding without sequelae, and the composite rate of additional non-scheduled exams and procedures due to vascular complications. The study included all patients who underwent atrial fibrillation ablation with radiofrequency (RF) between January 2020 and December 2022 in our center, performed by two expert operators: one utilizing a classic palpation (BLIND) approach and the second one employing the USG approach. Identical materials were used for access in both groups, and the choice of protamine administration or closure method was decided by the operator on a case by case basis. In total, there were 946 patients, 352 in USG group and 594 in BLIND group. For patients in both groups who were on vitamin K antagonists (VKAs), uninterrupted administration with an international normalized ratio (INR) ratio between 2.0 and 3.0 was required. Results Major complications were significantly reduced in the USG group compared to the BLIND group (0 (0%) in USG vs. 9 (1.5%) in BLIND, P = 0.02). No significant difference was observed in minor complications between the two groups (3 (0.8%) in USG vs. 6 (1.0%) in BLIND, P = 0.809). During hospitalization or readmission, 3 additional non-scheduled exams/procedures were required (3 vascular echos) in the USG group, while 33 were needed in the BLIND group (23 vascular echos, 6 thrombin injections, 2 surgical procedures and 2 CT-Angio) with a significative reduction (P 0.034). Conclusions USG venipuncture was associated with a reduction in major complication rates and a decrease in additional exams required during hospitalization or readmission. However, it did not lead to a reduction in minor complications. These findings support the use of ultrasound in AF ablation procedures to avoid access related complications requiring intervention.Baseline CharacteristicsSummary

Real-Time Detection of Circulating Thrombi in an Extracorporeal Circuit Using Doppler Ultrasound: In-Vitro Proof of Concept Study.

Thromboembolic stroke continues to be by far the most common severe adverse event in patients supported with mechanical circulatory assist devices. Feasibility of using Doppler ultrasound to detect circulating thrombi in an extracorporeal circuit was investigated. A mock extracorporeal circulatory loop of uncoated cardiopulmonary bypass tubing and a roller pump was setup. A Doppler bubble counter was used to monitor the mean ultrasound backscatter signal (MUBS). The study involved two sets of experiments. In Scenario 1, the circuit was sequentially primed with human blood components, and the MUBS was measured. In Scenario 2, the circuit was primed with heparinized fresh porcine blood, and the MUBS was measured. Fresh blood clots (diameter <1,000 microns, 1,000-5,000 microns, >5,000 microns) were injected into the circuit followed by protamine administration. In Scenario 1 (n = 3), human platelets produced a baseline MUBS of 1.5 to 3.5 volts/s. Addition of packed human red blood cells increased the baseline backscatter to 17 to 21 volts/s. Addition of fresh frozen plasma did not change the baseline backscatter. In Scenario 2 (n = 5), the blood-primed circuit produced a steady baseline MUBS. Injection of the clots resulted in abrupt and transient increase (range: 3-30 volts/s) of the baseline MUBS. Protamine administration resulted in a sustained increase of MUBS followed by circuit thrombosis. Doppler ultrasound may be used for real-time detection of circulating solid microemboli in the extracorporeal circuit. This technology could potentially be used to design safety systems that can reduce the risk of thromboembolic stroke associated with mechanical circulatory support therapy.

Association between intraoperative blood salvage and coagulation disorder after cardiopulmonary bypass

BackgroundThis study investigated whether intraoperative blood salvage was associated with coagulation disorder diagnosed by conventional coagulation tests and thromboelastography (TEG) after cardiopulmonary bypass (CPB).Study design and methodsThis was a prospective, observational study. Ninety-two patients who underwent cardiovascular surgery with CPB were enrolled. We evaluated coagulation function in patients with or without cell salvage blood transfusion at the following time points: before CPB, just after protamine administration, and 1 h after protamine administration. We evaluated platelet count, fibrinogen concentration, and TEG parameters. Patients were considered to have coagulation disorder if one or more of the following criteria were present: (1) residual heparin, (2) low platelet count, (3) low fibrinogen level, (4) low clotting factor level, and (5) hyperfibrinolysis.ResultsFifty-three of 92 patients (57.6%) received intraoperative cell salvage. Coagulation disorder was observed in 56 of 92 patients (60.9%) after CPB. There was no significant difference between patients with or without intraoperative blood salvage in terms of the incidence of coagulation disorder (p = 0.542) or the total volume of blood from the drain after CPB (p = 0.437). Intraoperative blood salvage was not associated with coagulation disorder diagnosed by either TEG or conventional coagulation tests (odds ratio 1.329, 95% confidence interval: 0.549–3.213, p = 0.547). There were no significant interactions between patients with or without intraoperative blood salvage regarding coagulation parameters derived from TEG.ConclusionsThe incidence of coagulation disorder and the total blood volume from the drain after CPB did not differ significantly between patients with or without intraoperative blood salvage.

Prevention and treatment of pericardial tamponade in the electrophysiology laboratory: a European Heart Rhythm Association survey.

Pericardial tamponade (PT) is the most frequent severe complication during electrophysiology (EP) procedures and requires immediate, co-ordinated, and effective treatment. However, multiple aspects of PT treatment are either not standardized or are under ongoing debate. An online questionnaire consisting of 26 multiple-choice questions was sent out to the European Heart Rhythm (EHRA) Research Network and also distributed via social media outputs. The EHRA survey was conducted between May and June 2023. A total of 213 replies were received from European (87%) and non-European countries. Ninety per cent of all participants perform interventions in dedicated EP labs equipped with different ablation platforms. In case of PT, most participants use X-ray as the main imaging modality guiding pericardial puncture, predominantly aiming for an anterior puncture site. Sheaths of different sizes are introduced into the pericardial space (84.3%), followed by a pigtail catheter. Application of protamine is an established but variable step in the majority (84.6%). Novel oral anticoagulants (NOAC) antidotes are not used by 73.3% of participants, while 15.2% routinely apply them. Re-transfusion of aspirated blood is performed by 72.1% [before protamine administration (18.2%), after protamine administration (13.5%), if pericardial effusion cannot be controlled (40.4%)]. A total of 72.4% re-transfuse without blood filter systems. A decision for surgical intervention is mostly taken if bleeding continues despite all interventional measures. The current survey demonstrates that the management of PT is heterogeneous among centres. The findings of this survey may help to guide operators in their treatment and decisions in the setting of PT.

Negative Effects Of Protamine On Myocardium In Paediatrics Patients Undergoing Cardiac Surgery Using A Cardiopulmonary Bypass Machine

The administration of protamine, a heparin reversal agent, is an integral part of cardiovascular bypass protocols, particularly in the post-bypass phase. In paediatric cases, protamine is administered in a titration dose. The use of protamine is associated with various adverse events, including myocardial impairment. Proper dosage adjustment is crucial during protamine administration, as excessive doses may result in the depression of myocardial function. Experimental studies examining protamine usage have revealed myocyte impairments, such as reduced myocyte contractility, dysfunction in signaling pathways, and alterations in cardiac receptors. Despite these findings, research on the impact of pediatric protamine on the myocardium remains limited and necessitates further investigation.

Advancing cardiotomy suction practices for coronary surgery via multidisciplinary collaborative learning

ObjectiveProfessional standards recommend stopping cardiotomy suction at the termination of cardiopulmonary bypass before protamine administration based on perceived safety concerns. This study evaluated a multidisciplinary collaborative quality-improvement intervention promoting this agreed-upon cardiotomy suction practice during coronary artery bypass grafting (CABG). MethodsA statewide intervention (eg, unblinded surgeon and perfusionist feedback, evidence-based lectures, evaluating barriers to change) involved 32 centers participating in the PERForm (ie, Perfusion Measures and Outcomes) Registry to standardize cardiotomy suction practices at cardiopulmonary bypass termination during CABG. Four non-Michigan registry participating centers were not exposed to collaborative learning. Cardiotomy suction practice was defined as the absence of or stopping cardiotomy suction before protamine administration. The practice changes attributed to the intervention, including Michigan and non-Michigan comparisons, were evaluated with the change of time effect modeled using splines. Multivariable regression was used to evaluate the intervention's associated impact (eg, mortality, reoperation, transfusion). ResultsAmong 10,394 patients undergoing CABG at Michigan centers, 80.7% achieved agreed-upon cardiotomy suction practices. The Michigan centers had nonsignificant changes in agreed-upon cardiotomy suction practices during the preintervention period (P = .24), with significant increased monthly change in practice thereafter, absent adjusted morbidity and mortality increases. The Michigan centers achieved a significantly greater adjusted monthly improvement in agreed-upon practices relative to non-Michigan centers within 7 months after the intervention (adjusted odds ratio for change of trends: 2.53, P < .001). ConclusionsThis initiative demonstrates the effectiveness of multidisciplinary collaborative quality improvement in advancing agreed-upon cardiotomy suction practices without negatively impacting clinical outcomes.

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

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. 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 60min 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. The total mean (95% CI) administered heparin dose in the 300U·kg-1, 400U·kg-1, and 500U·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. 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.

Platelet Function Testing Using Sonoclot and TEG6s as a Platelet Transfusion Prediction Tool in Open Heart Surgery.

Introduction The point-of-care test (POCT) is useful for blood coagulation management during cardiovascular surgery. Although thromboelastography (TEG6s) has been reported to have targeted benefits for blood transfusion in cardiac surgery, Sonoclot analysis has not yet been fully validated. In this study, we evaluated the accuracy of Sonoclot, especially platelet function (PF)as a platelet concentrate (PC) transfusion parameter, compared to TEG6s in cardiovascular surgery. Methods This single-center, prospective, randomised trial was conducted at a university hospital. Forty-two adult patients who underwent elective cardiac surgery requiring cardiopulmonary bypass were included in this study between 2017 and 2021. The participants were randomly assigned to the Sonoclot (S) or Sonoclot and TEG6s (ST) groups. The amount of intraoperative PC was determined according to the POCT parameter values at the time of protamine administration. In addition, we investigated the correlation between PF parameters of POCT and platelet count at the end of surgery. Results There was no statistically significant difference in the intraoperative PC volume between the two groups. The Sonoclot PF parameter, PF, was moderately correlated with platelet count at the end of surgery (r=0.5449, p=0.009), and the TEG6s PF parametershowed a strong correlation with platelet count at the end of surgery (r=0.7744, p<0.001). Conclusion There was no statistically significant difference in platelet transfusion volume between the Sonoclot and TEG6s in this study. The correlation between the PF of the Sonoclot and platelet count was moderate. This study suggests that PF of Sonoclot may be apotentiating indicator of PF.

Safety and efficacy of protamine administration for prevention of bleeding complications in patients with recent PCI undergoing TAVR

Abstract Background Despite major advances, TAVR is still associated with vascular and bleeding complications, that have an impact on mortality. Recent studies have shown that heparin antagonization using protamine resulted in lower bleeding rates in patients undergoing TAVR as compared to those without heparin reversal. However, there are only limited data on the safety of protamine regarding thromboembolic complications including in-stent thrombosis in TAVR patients who have had a recent PCI. Accordingly, daily practice varies between Centers. Purpose The aim of this multicentre study was to evaluate the safety and efficacy of protamine administration in patients who have had a recent PCI undergoing subsequent TAVR. Methods Our study included 1838 patients undergoing TAVI between 2017 and 2020. Of the patients included, 173 (9.4%) had a recent PCI (≤30 days), 319 (17.4%) had an intermediately (≥30 days) and 303 (16.5%) a previously performed PCI (≥6 months). Standardized vascular access management included the use of preclosure devices and PTA or implantation of a stent-graft, if necessary. The primary endpoint was a composite of one-year mortality and myocardial infarction at 30 days. Secondary endpoints included 30-day mortality and VARC-3-defined complications. Results The overall study population had a mean age of 81.1±6.2 years. Among patients with recent PCI, 134 (77.5%) patients received protamine for heparin reversal during the TAVR procedure. In the group of patients with intermediately and previously performed PCI 258 (80.9%) and 249 (82.2%) patients received protamine, respectively. In the recent PCI group, the occurrence of the primary endpoint was comparable between patients with protamine administration (24.6%) as compared to patients without heparin reversal (30.8%, p=0.53, Figure 1). Similarly, among patients with intermediately as well as previously performed PCI, the rates of the primary endpoint were comparable irrespective of protamine administration (20.1 vs 16.4%, p=0.59; 17.3 vs 27.7%, p=0.08, respectively, Figure 2). Moreover, among all three groups, the incidence of myocardial infarction at 30 days after TAVR was low and comparable between patients with and without heparin reversal (p&amp;gt;0.50). Overall, protamine administration was associated with decreased life-threatening bleeding (3.2 vs 9.4%, p&amp;lt;0.01) and major vascular complications (4.4 vs 7.9%, p=.02). Regarding safety endpoints, no overall differences were observed in the incidence of stroke between patients with and without protamine administration (1.5 vs 2.9%, p=0.13). Conclusion Protamine administration during the TAVR procedure did not increase the rate of myocardial infarction or one-year mortality in patients who have had a recently or intermediately performed PCI. Overall, heparin reversal using protamine resulted in significantly lower rates of life-threatening bleeding and major vascular complications, without increasing the incidence of stroke.Figure 1Figure 2

Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery on minimal invasive extracorporeal circulation; A prospective randomized study.

Individualized heparin and protamine management is increasingly used as a strategy to reduce coagulation activation and bleeding complications. While it is associated with increased heparin requirements during Cardiopulmonary Bypass (CPB), the impact on protamine administration remains controversial. We aim to investigate the effect of heparin level-guided monitoring on protamine dosing during cardiac surgery where low-anticoagulation protocols are implemented. This is a prospective, randomized, controlled trial. A total of 132 patients undergoing elective full-spectrum cardiac surgery with Minimal Invasive Extracorporeal Circulation (MiECC) were recruited. All patients were managed by the same anaesthetic, surgical and perfusion team. Patients were randomly allocated in two groups; the individualized heparin-protamine titration (IHPT) group and the conventional heparinization and reversal group by using ACT (cACT) with a 0.75:1, protamine: heparin ratio. Titration was accomplished with the Hepcon HMS Plus (Medtronic, Minneapolis, MN) system. The primary outcome of the study was the total protamine dose used. Secondary outcomes comprised of the total heparin dose, the percentage of patients achieving target ACT, 24-h transfusion requirements, postoperative bleeding, duration of mechanical ventilation, major morbidity and length of hospital stay. Patients in each group were divided in two subgroups according to the target ACT; those operated for coronary artery bypass grafting (CABG) using a target ACT >300s and the rest (non-CABG) patients operated with a target ACT >400s, respectively. Protamine requirements were significantly reduced when IHPT was implemented; CABG (118 ± 24mg vs 163 ± 61 mg; p < 0.001) and non-CABG cases (151 ± 46mg vs 197 ± 45mg; p < 0.001). Moreover, heparin requirements were significantly higher in the non-CABG subgroup managed with IHPT (34,539 ± 7658 IU vs 29,893 ± 9037 IU; p = 0.02). In overall, no significant differences were detected with respect to postoperative bleeding, transfusion of RBC or other blood products. Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery with MiECC implementing reduced anticoagulation strategy. clinicaltrials.gov; NCT04215588.

Albumin and Cardioprotection in On-Pump Cardiac Surgery—A Post Hoc Analysis of a Randomized Trial

To study the quantitative potency of plasma albumin on cardioprotection in terms of creatinine kinase-myocardial band mass (CK-MBm) in on-pump cardiac surgery. Post hoc analysis of a double-blinded randomized clinical trial. Single-center study in the Helsinki University Hospital. A total of 1,386 adult on-pump cardiac surgical patients. Administration of 4% albumin (n = 693) or Ringers acetate (n = 693) for cardiopulmonary bypass priming and volume replacement intraoperatively and postoperatively during the first 24 hours. Albumin concentration was measured preoperatively and intraoperatively (after protamine administration), and CK-MBm on the first postoperative morning. Multivariate linear regression analyses were measured in the whole cohort and the Ringer group. Plasma albumin concentration did not differ between the groups preoperatively (Ringer v albumin: 38.3 ± 5.0 g/L v 38.6 ± 4.5 g/L; p = 0.171) but differed intraoperatively (29.5 ± 5.2 g/L v 41.5 ± 6.0 g/L; p < 0.001). Creatinine kinase-myocardial band mass was higher in the Ringer (32.0 ± 34.8 μg/L) than in the albumin group (24.3 ± 33.0 μg/L) (p < 0.001). Aortic cross-clamping time associated with CK-MBm in the whole cohort (standardized β = 0.376 [95% CI 0.315-0.437], p < 0.001) and the Ringer group (β = 0.363 [0.273-0.452]; p < 0.001). Albumin administration in the whole cohort (β = -0.156 [-0.201 to -0.111]; p < 0.001) and high intraoperative albumin concentration in the Ringer group (β = -0.07 [-0.140 to -0.003]; p = 0.04) associated with reduced CK-MBm. Compared with ischemia-induced increase in CK-MBm, albumin's potency to reduce CK-MBm was 41% in the whole cohort (β-value ratio of -0.156/0.376) and 19% in the Ringer group (β-value ratio of -0.07/0.363). Both endogenous and exogenous albumin appear to be cardioprotective regarding CK-MBm release in on-pump cardiac surgery.