Protamine Administration Research Articles

The emerging role of adopting protamine for reducing the risk of bleeding complications during the percutaneous coronary intervention: A meta-analysis.

The safety and the benefits of reducing the risk of bleeding complications via protamine administration during the percutaneous coronary intervention (PCI) remains unclear. This study aimed to systematically assessed the efficacy and safety of using protamine in PCI. Potential academic studies were identified from PubMed, Cochrane Library, EMBASE, and Web of Science. The time range we retrieved from was that from the inception of electronic databases to March 31, 2022. Gray studies were identified from the references of included literature reports. Stata version 12.0 statistical software (StataCorp LP) was used to analyze the pooled data. A total of seven studies were involved in our study. The overall participants of the protamine group were 4983, whereas it was 1953 in the nonprotamine group. This meta-analysis indicated that protamine was preferable for PCI as its lower value of major bleeding (odds ratio [OR] = 0.489, 95% confidence interval [CI]: 0.362-0.661, p < .001) and minor bleeding (OR = 0.281, 95% CI: 0.123-0.643, p = .003). Additionally, the protamine did not tend to be related a higher incidence of mortality (p = .143), myocardial infarction (p = .990), and stent thrombosis (p = .698). Based on available evidence, use of protamine may reduce the risk of bleeding complications without increasing the risk of mortality, myocardial infarction, and stent thrombosis. Given the relevant possible biases in our study, adequately powered and better-designed studies with long-term follow-up are required to reach a firmer conclusion.

Abstract 12642: Protamine Administration in Patients Undergoing Percutaneous Left Atrial Appendage Occlusion

Introduction: Intravenous protamine sulfate is widely used to reverse anticoagulation after structural heart interventions. Protamine is currently designated as in shortage by the US FDA, and its use has potential adverse events such as anaphylaxis, thrombosis, and stroke. There is limited data on the safety and efficacy of heparin reversal with protamine after left atrial appendage occlusion (LAAO). Hypothesis: We hypothesize that patients who received protamine for heparin reversal after percutaneous LAAO have no changes in bleeding complication rates versus patients who did not receive protamine. Methods: This retrospective study included 242 atrial fibrillation patients with a high risk of stroke and bleeding who received percutaneous LAAO between January 2020 and November 2021. The primary outcome assessed was life-threatening, disabling, or major bleeding within 48 hours following the procedure. Secondary outcomes included major adverse cardiac events (MACE) within 48 hours, minor bleeding events, MACE, device-related thrombosis or pericardial effusion within 45 days, and RBC transfusions. Patients with peri-procedure complications including pericardial effusion and/or thrombosis were excluded. Baseline characteristics were compared between both cohorts. Results: No significant difference in the primary outcome was observed between patients who received protamine compared to those who did not (5.8% vs 4.9%, p-value 0.57). There was significantly more minor bleeding in patients who did not receive protamine (0.6% vs 4.9%, p-value 0.05). MACE within 48h following the procedure, MACE, device-related thrombosis or pericardial effusion within 45 days, and RBC transfusions were comparable between the two cohorts, as described in table 2. Conclusions: Protamine administration for heparin reversal did not affect rates of life-threatening, disabling, or major bleeding complications in patients who underwent percutaneous LAAO.

Optimal protamine-to-heparin dosing ratio for the prevention of bleeding complications in patients undergoing TAVR – a multicentre experience

Abstract Background Despite major advances, transcatheter aortic valve replacement (TAVR) is associated with procedure-related vascular and bleeding complications, that have a significant impact on mortality. A recently published study has shown that heparin antagonization using protamine resulted in significantly lower rates of serious bleeding events in patients undergoing TAVR as compared to those without heparin reversal. However, the optimal protamine-to-heparin dosing ratio to prevent bleeding complications without increasing ischemic complications in patients undergoing TAVR is unknown. Accordingly, daily clinical practice varies between selective to routine administration of protamine in different dosing ratios. Purpose The aim of this observational multicentre study was to compare the safety and efficacy of two different protamine-to-heparin dosing ratios for the prevention of bleeding complications after TAVR. Methods The study included 1446 patients undergoing TAVR, of whom 623 (43.1%) received partial and 823 (56.9%) full heparin antagonization (0.4–0.6 mg versus 0.9–1.0 mg protamine/100 units of heparin). The indication for partial or full heparin antagonization was left to the discretion of the operator, who made the decision according to the patient's individual thrombotic and bleeding risk. The primary endpoint was a composite of 30-day mortality, life-threatening and major bleeding. Safety endpoints included stroke and myocardial infarction at 30 days. Results The overall study population had a mean age of 81.1±6.0 years; 47.9% were of female gender. The baseline characteristics were well balanced between the two groups. Full antagonization of heparin resulted in significantly lower rates of the primary endpoint as compared to partial heparin reversal (5.6 vs. 10.4%, p&amp;lt;0.01), mainly driven by lower rates of life-threatening (0.5 vs 1.6%, p=0.05) and major bleeding (3.2 vs 7.5%, p&amp;lt;0.01). The incidence of major vascular complications was significantly lower in patients with full heparin reversal (3.5 vs 7.5%, p&amp;lt;0.01), as presented in Figure 1. Accordingly, the post-interventional drop in hemoglobin level and the need for red-blood-cell transfusion was lower in patients receiving full as compared to partial heparin reversal (1.5±1.2 vs 1.7±1.2 g/dl, p&amp;lt;0.01; 10.4 vs 15.9%, p&amp;lt;0.01, respectively). Regarding safety endpoints, no differences were observed in the incidence of stroke and myocardial infarction between the groups (2.2 vs 2.6%, p=0.73 and 0.2 vs 0.4%, p=0.64, respectively). Multivariate regression analyses revealed that full antagonization of heparin (OR: 0.43 [95% CI: 0.24–0.81], p&amp;lt;0.01) was independently associated with the primary end point Conclusion Full heparin antagonization resulted in significantly lower rates of life-threatening and major bleeding after TAVR as compared to partial heparin reversal. The occurrence of stroke and myocardial infarction was low and comparable between both groups. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation).

Transit-time flow measurement parameters after protamine infusion in CABG surgeries.

The objective of this study is to evaluate protamine sulfate effects on graft's blood flow by comparing transit-time flow measurement (TTFM) values before and after protamine administration. This is an observational study with data collected between years 2018 and 2020. Immediate graft patency was evaluated using TTFM. Only patients with TTFM parameters registered before and after protamine infusion were included. The main three parameters studied were: mean graft flow (MGF), pulsatility index (PI), and diastolic flow (DF). In the first analysis, all conduits were evaluated regardless of the surgical technique used. In a second analysis, on-pump and off-pump groups were compared. Evaluated grafts were left internal thoracic artery, saphenous vein graft (SVG), radial artery, and right internal thoracic artery. Since SVG was numerically the most used graft, an exclusive analysis was created. Our study included 575 patients, resulting in a total of 1686 grafts, mean 2.93 grafts/patient. Off-pump surgery was performed in 158 patients. Before protamine infusion, inadequate TTFM parameters were observed in 3.8% of grafts. Overall, after protamine administration, MGF decreased in all grafts, but its reduction was not statistically significant. PI values increased in the SVG and DF values reduced in LIMA grafts. SVG group analysis showed that after protamine PI values were higher in OM1 and RCA. DF values increased in RCA. The comparison between off and on-pump surgeries, showed that in off-pump cases TTFM measures did not present statistically significant differences. Significant variations were observed in TTFM values before and after protamine administration. Although different, those values remained within the normal reference ranges. We recommend that flow measurement should be performed before protamine infusion.

Rotational Thromboelastometry Values After On-Pump Cardiac Surgery - A Retrospective Cohort Study.

Viscoelastic coagulation monitoring is recommended for coagulation management after cardiac surgery, but optimum target values are poorly defined. To determine "to-be-expected" values in rotational thromboelastometry (ROTEM) after heparin reversal, to correlate ROTEM parameters with fibrinogen levels and platelet count, and to estimate the effect of hemoglobin levels on these measurements. We retrospectively analyzed 571 consecutive adult patients undergoing cardiac surgery with cardiopulmonary bypass from 12/2018 to 08/2020. ROTEM and conventional laboratory measurements were performed 5 to 10 minutes after protamine administration. Clotting times in EXTEM, INTEM, and FIBTEM were significantly prolonged (72.6%, 96.1%, and 31.8% above reference ranges, respectively). Clot firmness parameters in EXTEM and INTEM were relevantly reduced (7.9% to 14.4% and 9.1% to 32.3% below the reference ranges, respectively). There was an excellent linear correlation of FIBTEM amplitude after 10 min (A10) and of maximal clot firmness (MCF) with fibrinogen concentrations (r = .81 and .80). Areas under receiver operating characteristic (AUROC) for identifying hypofibrinogenemia <1.5 g/L were between .80 and .87. No effect of hematocrit was observed. We also found a linear correlation of EXTEM, INTEM, and EXTEM-FIBTEM at both A10 and MCF with platelet counts (.32 to .68). The AUROCs for identifying thrombocytopenia (<100,000/μL) were .79 to .84, and were greater for A10 than for MCF measurements (P=.074, .001, and <.001, respectively). "To-be-expected" ROTEM values after CPB are different from the published reference ranges. ROTEM parameters might allow for reliable estimation of fibrinogen level and platelet count without being influenced by hematocrit.

The Use of Protamine During Peripheral Vascular Interventions in the Vascular Quality Initiative

Protamine administration was shown to reduce bleeding after carotid surgery, but the role of protamine during peripheral vascular interventions (PVI) remains unknown. This study evaluates the trend and outcomes of protamine use in the Vascular Quality Initiative. Our hypothesis is that the use of protamine is associated with decreased bleeding after PVI.

Safety and efficacy of immediate heparin reversal with protamine after complex percutaneous coronary intervention

BackgroundCompared to simple percutaneous coronary intervention (PCI), complex PCI is associated with higher bleeding and thrombotic risk. No previous study has evaluated the use of protamine after PCI with contemporary technologies. This study aimed to evaluate the safety and efficacy of manual compression with and without protamine after transfemoral complex PCI.MethodsWe retrospectively analyzed 160 patients (protamine group, n = 92; non-protamine group, n = 68) who underwent complex PCI via the femoral artery. The primary outcome was a composite of in-hospital death, myocardial infarction, stent thrombosis, stroke/systemic embolism, bleeding requiring blood transfusion, and vascular access complications.ResultsThe primary outcome was significantly lower in the protamine group than in the non-protamine group (4.3% vs. 17.6%; p = 0.006). This was driven mainly by the lower incidences of hematoma in the protamine group (3.3% vs. 13.2%, p = 0.020). Furthermore, the protamine group had a significantly shorter hospital stay than the non-protamine group (4.8 ± 3.7 days vs. 8.4 ± 8.3 days, p = 0.001). While > 90% of the patients had acute coronary syndrome, there were no incidences of myocardial infarction or stent thrombosis in either group.ConclusionsAmong patients who underwent complex PCI via transfemoral access, immediate protamine administration was associated with a significantly lower rate of vascular access complications, especially hematoma, and shorter hospital stay than no protamine administration.

A S tudy of the Effectiveness of Lidocaine to Treat S evere P ulmonary Vascular Constriction induced by Protamine

Abstract Background: Protamine neutralises heparin after separation from cardiopulmonary bypass. This study aimed to evaluate the effects of lidocaine on protamine induced pulmonary vascular constriction in paediatric cardiothoracic surgery. Methods: This was a single-centre, prospective, double-blind and randomised study conducted among eighty pediatric patients with acyanotic congenital cardiac disease, scheduled for elective on-pump cardiac surgery under general anaesthesia. In the study, the participants were divided into four groups: Group NPHL- nonpulmonary hypertension with lidocaine preconditioning, group NPHS- nonpulmonary hypertension with normal saline (as placebo), group PHL- pulmonary hypertension with lidocaine preconditioning, and group PHS- pulmonary hypertension with normal saline (as placebo). Results: Pulmonary vasoconstriction occurred in 11.25% of cases after protamine administration. Both the NPHS and PHS groups exhibited an increase in mean airway pressure (Paw), Respiratory index (RI), alveolar-arterial oxygen difference (A-aDO2), pulmonary artery pressure (PAP) and decreased dynamic pulmonary compliance (Cydn) and oxygen index (OI) after protamine administration. However, these changes were not observed in the NPHL and PHL groups with lidocaine preconditioning. Plasma levels of TXB2 in the NPHS and PHS groups were higher than the NPHL and PHL groups, but 6-keto-PGF1 alpha levels were lower in the NPHS and PHS groups than in the NPHL and PHL groups. Conclusion: In congenital heart disease, repair without cardiopulmonary bypass is not possible in most cases. Prior to reversing heparin with protamine, preconditioning lidocaine reverses protamine-induced pulmonary vasoconstriction and improves lung function.

Hemodynamic Effects of Protamine Infusion in Dogs with Myxomatous Mitral Valve Disease Undergoing Mitral Valvuloplasty.

Protamine, an antagonizing agent to heparin, is indispensable for dogs undergoing cardiopulmonary bypass. Protamine-induced hypotension (PIH) during cardiac anesthesia has been reported in humans. The purpose of this study was to describe the hemodynamic effect of protamine administration in dogs during cardiac surgery in clinical cases. Study design: Retrospective, clinical, cohort study. A total of 14 client-owned dogs who suffered heart failure due to medically uncontrolled myxomatous mitral valve disease (MMVD) were included in this study. The severity of MMVD was classified according to American College of Veterinary Internal Medicine staging (ACVIM: stage B2, C, D) and dogs undergoing mitral valve surgery. Records with clinical data for dogs treated between July 2019 to August 2020 were examined for age, sex, breed, body weight, concurrent diseases, hospitalization, anesthetic record, and mortality within 3 months after the operation. PIH was defined as mean arterial pressure (MAP) lowered by 20% of that before protamine infusion. To evaluate the effect of protamine on hemodynamic variables, each of the other values was compared with values at the beginning of protamine infusion. MAP decreased by 41.0 and 45.7% in two dogs (14.3%) compared with pressure before protamine infusion. Others did not show obvious alteration in hemodynamic variables. Epinephrine treatment alleviated hypotension in one dog. Another dog with systemic hypotension concomitant with elevated central venous pressure did not respond to epinephrine treatment and a reboot of extracorporeal circulation was required. Reheparinization and reinstitution of cardiopulmonary bypass successfully resuscitate the second dog. In conclusion, clinicians should alert the incidence of severe hypotension even with slow protamine infusion following canine cardiac surgery. This study also provides two effective treatments for catastrophic hypotension during protamine infusion.

Apical closure device for full-percutaneous transapical structural and valve procedures with large-sized introducer sheaths: The final preclinical study.

Closed-chest transapical valve implantations (aortic, mitral, and tricuspid) and cardiac structural procedures requiring large-sized introducer sheaths cannot be safely performed with the available technology. We tested a self-expanding apical closure device in a closed-chest animal model, using large-sized introducer sheaths and human-sized animals to establish the technique for future tests in humans. Six human-sized pigs (mean weight: 89.7 ± 3.7 kg) received general anesthesia, intubation, and full heparinization (15,000 IU/animal; expected activated clotting time >200 s). Under fluoroscopy and multimodality imaging guidance with next-generation fusion imaging prototypes, a 15-cm long needle and a standard guidewire were percutaneously inserted under the xiphoidal aponeurosis and into the ventricular apex. After the exchange with a stiff guidewire, a 21-Fr introducer sheath for transapical procedures (outer diameter: 25-Fr) was placed in the left ventricle through the apex. The self-expanding closure device was inserted and deployed under fluoroscopic guidance while the 21-Fr sheath was gently removed. Hemodynamic conditions were monitored for 30 min and then the chest was opened to inspect the closure device and quantify the blood loss in the pericardium. Animals were killed and the hearts were removed and inspected. All six apical closure devices were successfully deployed without adverse events. No death, hemodynamic collapse, or cardiac tamponade occurred during the 30-minobservational period (mean systolic and diastolic pressures: 88 ± 11 and 58 ± 13 mmHg, respectively; mean heart rate: 60 ± 11 beats per minutes). Pre- and postdeployment (after protamine administration) mean activated clotting time was 541 ± 263 and 217 ± 62 s, respectively. The plugs provided good sealing with a mean of 27.2 ± 13.86 ml of blood lost in the pericardium. Postmortem inspection showed good plug fixation without myocardial damage. This self-expanding apical closure device successfully sealed the percutaneous access sites made with large-sized introducer sheaths in human-sized animals. This preclinical study suggests that transapical valve and structural procedures requiring large-sized introducer sheaths can be performed percutaneously.

Initial results from an enhanced recovery program for pediatric cardiac surgical patients.

Over recent years, a number of enhanced recovery programs have appeared in first, adult colorectal surgery, and subsequently many other adult surgical specialties. Increasing interest in this approach to perioperative management in children culminated in the recent development of the first enhanced recovery pathway for pediatric intestinal surgery, endorsed by Enhanced Recovery after Surgery Society (ERAS®). In parallel, there has been increasing interest in the refinement of perioperative management of selected pediatric cardiac surgical patients, invariably referred to as "fast track" management. Initiatives have largely focused on duration of postoperative ventilation rather than on a much wider range of perioperative interventions to optimize recovery and ensure timely discharge after surgery. In our institution, a "Level 1" pediatric cardiac surgical center, we assembled a multidisciplinary team to design a comprehensive enhanced recovery pathway, based on ERAS® methodology, for selected cardiac surgical patients. After a lengthy period of planning, staff education, and preparation, we implemented the pathway at the end of November 2019. We conducted a prospective audit of the perioperative management and outcomes of the first 88 patients managed according to this enhanced recovery pathway over a 25-month period in our institution. The mean age of the patients was 5.8years (range 0.5-17.9), and the mean weight was 22.4kg (range 6.6-57.2). Sixty-eight of the 88 patients were cardiopulmonary bypass cases. A total of 54% of patients received all four defined intraoperative anesthetic interventions (intravenous paracetamol, non-steroidal anti-inflammatory drug, antiemetic if aged more than 4years, and use of a local anesthetic technique). A total of 89% of patients met the target extubation time of 6h after administration of protamine. Median postoperative intensive care unit length of stay was 23.5h (range 15.2-89.5). When compared to a historic control group, this represented a 22% reduction in median intensive care unit stay, although the total hospital length of stay remained unchanged. A total of 83% of patients met the target hospital discharge target of the fifth postoperative day. These preliminary results suggest that enhanced recovery pathway implementation for selected pediatric cardiac surgical patients is feasible, with acceptable outcomes. They suggest areas for further development and the potential for wider implementation.

Abstract No. : ABS3567: The feasibility and impact of acute normovolaemic haemodilution in on-pump cardiac surgery: a descriptive study

Background & Aims:Cardiac surgeries have the potential of perioperative blood loss, allogenic blood transfusion, prolonged postoperative hospitalstay and thus increase the load on the blood bank in the hospital. We evaluated the feasibility and impact of acute normovolaemic haemodilution (ANVH) in on-pump cardiac surgery.Methods:The data of 195 patients undergoing on-pump cardiac surgeries (coronary artery bypass graft surgeries, single/double valve repair surgeries) was retrospectively retrieved. Pre-operative haemoglobin >12 gm % was taken as criteria for ANVH. The amount of blood withdrawn was replaced withcrystalloid in a 1.5:1 ratio. The noradrenaline 4 µg/ml bolus was used to maintain the haemodynamics if required. The bloodwas re-transfused after protamine administration. The threshold for autologous blood transfusion was taken as <8 gm/dl.Results:In 75.38% (147) patients, ANVH was carried out. The mean pre-operative haemoglobin of patients who underwent ANVH was 13.5 gm%. An average of 1.44 units of blood was withdrawn. Allogenic blood transfusion was required in 23.40% of patients.Six patients were re-explored for surgical cause and excluded from the analysis. Mean 0.5 units of packed red blood cells (PRBC) were transfused in the post-operative period. The haemodynamics were maintained during ANVH.Conclusion:ANVH is feasible in the majority of patients, drastically reduces the requirement of allogenic blood transfusion in patients undergoing on-pump cardiac surgeries without much problem in maintaining haemodynamics.

Comparison of coagulation monitoring using ROTEM and Sonoclot devices in cardiac surgery: a single-center prospective observational study.

Viscoelastic tests (VETs) are recommended during cardiac surgery to monitor coagulation status and guide transfusion. We compared the results of two VETs, the Sonoclot Analyzer and the ROTEM Sigma. Agreement between viscoelastic tests' subdiagnoses and overall diagnosis severity was assessed. Correlations with conventional coagulation tests (CCT) and the discriminatory potential of numerical VET outputs for transfusion thresholds was determined. Single-center, prospective observational study in a tertiary academic center. In fifty adult patients undergoing elective cardiac surgery, parallel Sonoclot, ROTEM and CCT analysis was performed before heparin, or after protamine or coagulation product administration. All patients completed the study, resulting in 139 data points. Agreement on the severity of coagulation disorders was acceptable (83%), but poor (27%) on the differentiation of the underlying causes. Correlations between ROTEM parameters and CCT were good (postprotamine: FIBTEM A5 (r2=0.90 vs. fibrinogen) and EXTEM-FIBTEM A5 difference (r2=0.81 vs. platelet count). Sonoclot correlated less (Clot Rate (r2=0.25 vs. fibrinogen) and Platelet Function (r2=0.43 vs. platelet count). This was reflected in the discriminatory potential of these parameters as found by linear mixed modelling. We suggest clinically useful grey zones for VET cutoff interpretation. ROTEM and Sonoclot accord well on the detection of severity of coagulation dysfunction, but not on the diagnosis of the underlying cause. ROTEM correlated more closely with CCT then Sonoclot. We propose a testing strategy that could lead to a cost-effective approach to the bleeding cardiac surgery patient.

Platelet Dysfunction in Cardiac Surgery: When is the Best Time to Assess It? An Observational Single Center Study.

Purpose. Cardiac surgery is characterized by a high risk of complications related to perioperative bleeding. Guidelines suggest the use of local algorithms based on perioperative point-of-care tests to assess and manage potential coagulation abnormalities. We investigated whether heparin reversal administration affects the adenosine-5-diphosphate (ADP) test values, thus identifying the earliest time point following cardio-pulmonary bypass that permits the promptest detection and treatment of potential platelet dysfunctions. Methods. This was a retrospective, single-center, observational study enrolling cardiac surgery patients requiring cardiac bypass. ADP-tests at 4 different time-points during surgery (T0: baseline, T1: at aortic de-clamping, T2: 10minutes after protamine administration, and T3: at the end of surgery) were performed. Results. 63 patients undergoing elective cardiac surgery were studied. Baseline ADP-test values were almost constantly greater than intraoperative values, and end of surgery values were often greater than previous intraoperative values. The only difference that proved to be not statistically significant was between T1 and T2, with a clinically insignificant mean difference of -.2 U (95%CI of difference: -6.9 - 6.5 U). There was no correlation between the variation in ADP-test values pre- and post-protamine administration and the protamine-to-heparin ratio. Conclusion. The results of the present study support the hypothesis that the ADP-test could be performed early, at aortic de-clamping before protamine administration. This approach allows for the promptest assessment of a potential impairment in platelet function, and its timely correction.

Evaluation of health outcomes after the implementation of rotational thromboelastometry in patients undergoing cardiac surgery

Background Viscoelastic tests (rotational thromboelastometry, ROTEM®), together with the implementation of a specific algorithm for coagulation management in cardiac surgery, enable perioperative coagulopathy to be better controlled. Methods Retrospective cohort study including 675 patients who underwent cardiac surgery with cardiopulmonary bypass. The incidence of allogeneic blood transfusions and clinical postoperative complications were analyzed before and after ROTEM® implementation. Results Following viscoelastic testing and the implementation of a specific algorithm for coagulation management, the incidence of any allogeneic blood transfusion decreased (41.4% vs 31.9%, p = .026) during the perioperative period. In the group monitored with ROTEM®, decreased incidence of transfusion was observed for packed red blood cells (31.3% vs 19.8%, p = .002), fresh frozen plasma (9.8% vs 3.8%, p = .008), prothrombin complex concentrate administration (0.9% vs 0.3%, p = .599) and activated recombinant factor VII (0.3% vs 0.0%, p = .603). Increased incidence was observed for platelet transfusion (4.8% vs 6.8%, p = .530) and fibrinogen concentrate (0.9% vs 3.5%, p = .066), tranexamic acid (0.0% vs 0.6%, p = .370) and protamine administration (0.6% vs 0.9%, p = .908). Similar results were observed in the postoperative period, but with a decreased incidence of platelet transfusion (4.8% vs 3.8%, p = .813). In addition, statistically significant reductions were detected in the incidence of postoperative bleeding (9.5% vs 5.3%, p = .037), surgical reexploration (6.0% vs 2.9%, p = .035), and length of Intensive Care Unit (ICU) stay (6.0 days vs 5.3 days, p = .026). Conclusions The monitoring of hemostasis by ROTEM® in cardiac surgery, was associated with decreased incidence of allogeneic blood transfusion, clinical hematologic postoperative complications and lengths of ICU stay.

Emergency Department Management of Acute Venous Thromboembolism in Patients With Obesity With Intravenous Unfractionated Heparin and Anti-Xa Monitoring

Background: Unfractionated heparin (UFH) remains a frequently utilized agent in the emergency department (ED) for management of acute venous thromboembolism (VTE). While various protocols of UFH dosing have been proposed for patients with obesity, the optimal dosing and monitoring strategy is unclear. Objective: This study aims to compare the time to the first therapeutic anti-Xa level in obese acute VTE patients following the use of either total body weight (TBW) or adjusted body weight-based (AdjBW) dosing of UFH in the ED, and to analyze the impact of different dosing strategies on patient outcomes. Methods: Inclusion criteria included adult patients with a BMI > 30 kg/m2, and suspected VTE managed with UFH per institutional protocol utilizing a bolus dose followed by maintenance infusion and anti-Xa monitoring. The primary outcome was time to the first therapeutic anti-Xa level in the group dosed per TBW compared with the group dosed per AdjBW. Safety outcomes included incidence of bleeding events, protamine administration, and mortality. Results: There were 32 patients included in the study. Patients dosed per TBW achieved a median time to first therapeutic anti-Xa level of 14.5 hours compared with 15 hours in the AdjBW group (P = .613). The median therapeutic UFH infusion rate was 16 units/kg/hr in the TBW group compared with 13.5 units/kg/hr in the AdjBW group (P < .001). Safety outcomes were not significantly different between groups. Conclusion: Patients presenting to the ED with acute VTE may be managed with UFH using either a TBW or AdjBW dosing strategy.

Efficacy of point-of-care thromboelastography 6s to evaluate platelet function in a patient with pseudothrombocytopenia undergoing cardiopulmonary bypass: a case report

BackgroundPseudothrombocytopenia is a phenomenon caused by in vitro platelet aggregation induced by anticoagulants contained in blood sampling tubes. Thromboelastography (TEG) 6s is a common point-of-care viscoelastic test to assess intraoperative coagulation status, which may reduce the need for blood transfusions. The reliability and usefulness of TEG6s for patients with pseudothrombocytopenia has not been established.Case presentationWe present a patient with pseudothrombocytopenia, who underwent suprarenal abdominal aortic aneurysm repair under cardiopulmonary bypass. At the beginning of surgery, TEG6s with citrated blood sampling showed that the results were unaffected by the disease. After completion of the aortic repair and the administration of protamine, maximum amplitude of TEG6s and adequate hemostasis were achieved without platelet transfusions, while standard laboratory tests showed thrombocytopenia.ConclusionsIn the present patient who underwent cardiopulmonary bypass, TEG6s may have contributed to a reliable and useful assessment of coagulation and hemostatic status avoiding unnecessary platelet transfusions.

Periprocedural outcomes of protamine administration after catheter ablation of atrial fibrillation.

Perioperative anticoagulation management with uninterrupted or minimally interrupted anticoagulation during atrial fibrillation (AF) ablation is thought to be critical to minimize thromboembolic complications. Protamine is often administered to neutralize the effects of heparin and expedite vascular hemostasis post-procedure. We performed a systematic review and meta-analysis to determine the effectiveness of protamine to expedite vascular hemostasis and ambulation in patients undergoing AF ablation. Electronic searches on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through August 7, 2021, were performed. The primary outcomes included-time to hemostasis (minutes) and time to ambulation (minutes). The secondary outcomes included - any vascular complications (excluding minor hematoma), minor hematoma, or cerebrovascular accidents (CVA). A total of 5 eligible studies (3 retrospective cohort studies and two randomized trials) consisting of 1012 patients (515 patients received protamine group and 497 patients did not receive protamine group) were included in the meta-analysis. There was a significant reduction in time to ambulation [weighted mean difference (WMD) -176.6 minutes, 95% Confidence interval (CI) -266.9 to -86.3; p < 0.01] and time to hemostasis (WMD -13.72 minutes, 95% CI -22 to -5.4, p < 0.01) in the protamine group compared to the contrary. At a follow-up up to 3 months, there was no statistical difference between the two groups with regards to vascular complications (2.9% vs. 7.4%; Risk ratio (RR) 0.46 95% CI 0.17 to 1.24; p = 0.12), minor hematoma (2.1% vs. 5.8%; RR 0.43, 95% CI 0.16 to 1.2; p = 0.11) or CVA (0 vs. 0.3%; RR 0.62, 95% CI 0.08 to 4.98; p = 0.65). Protamine administration was associated with reduced time to ambulation (176 minutes reduction) and time to hemostasis (13 minutes reduction) without an increase in any adverse events.

A Pharmacokinetic and Plasmin-Generation Pharmacodynamic Assessment of a Tranexamic Acid Regimen Designed for Cardiac Surgery With Cardiopulmonary Bypass

To examine the pharmacokinetics (PK) and pharmacodynamics of a tranexamic (TXA) regimen designed for cardiac surgery with cardiopulmonary bypass (CPB). A pilot study quantifying TXA concentrations, fibrinolysis markers, and a plasmin- generation (PG) assay. For comparison, PG assay was performed on pooled normal plasma (PNP) with varying TXA concentrations. A single-center, tertiary, academic medical center. Twenty patients undergoing cardiac surgery with CPB for valve surgery and/or coronary artery bypass grafting. TXA 100 mg/h infusion for 5 hours starting before incision; 1 g TXA in CPB prime and 1 g TXA at CPB end prior to heparin reversal. The PK fit a 2-compartment disposition model. TXA concentrations were above 15 mg/L in all patients during CPB through 2 hours post-TXA infusion. During and after CPB, the TXA regimen decreased the median peak PG by 60% (95% confidence interval [CI], 56%-62%). Lowest median peak PG occurred 15 minutes postprotamine. Peak median D-dimer level of 1.24 (0.95-1.71; 95% CI) mg/L occurred at 15 minutes postprotamine and baseline-adjusted ΔD dimer correlated with increased CPB time (p=0.004) and lower TXA level (p=0.001). The median 24-hour chest tube output was 447 (330-664; 95% CI) mL. PG assay on PNP revealed a plateau inhibition at 5 mM TXA (786 mg/L). This regimen, with total perioperative dose of 2.5 grams, provided TXA concentrations above 15 mg/L for all patients from CPB initiation through 2 hours post-TXA. PG was significantly inhibited (p < 0.0001) during and after CPB, with maximum inhibition measured at 15 minutes after protamine administration.

Efficacy of Pulsatile Flow Perfusion in Adult Cardiac Surgery: Hemodynamic Energy and Vascular Reactivity.

Background: The role of pulsatile (PP) versus non-pulsatile (NP) flow during a cardiopulmonary bypass (CPB) is still debated. This study’s aim was to analyze hemodynamic effects, endothelial reactivity and erythrocytes response during a CPB with PP or NP. Methods: Fifty-two patients undergoing an aortic valve replacement were prospectively randomized for surgery with either PP or NP flow. Pulsatility was evaluated in terms of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE). Systemic (SVRi) and pulmonary (PVRi) vascular resistances, endothelial markers levels and erythrocyte nitric-oxide synthase (eNOS) activity were collected at different perioperative time-points. Results: In the PP group, the resultant EEP was 7.3% higher than the mean arterial pressure (MAP), which corresponded to 5150 ± 2291 ergs/cm3 of SHE. In the NP group, the EEP and MAP were equal; no SHE was produced. The PP group showed lower SVRi during clamp-time (p = 0.06) and lower PVRi after protamine administration and during first postoperative hours (p = 0.02). Lower SVRi required a higher dosage of norepinephrine in the PP group (p = 0.02). Erythrocyte eNOS activity results were higher in the PP patients (p = 0.04). Renal function was better preserved in the PP group (p = 0.001), whereas other perioperative variables were comparable between the groups. Conclusions: A PP flow during a CPB results in significantly lower SVRi, PVRi and increased eNOS production. The clinical impact of increased perioperative vasopressor requirements in the PP group deserves further evaluation.