Protamine Administration Research Articles

Platelet Function Test in Coronary Artery Bypass Grafting: Does It Predict Postoperative Bleeding?

Abstract Background Patients undergoing on-pump coronary artery bypass grafting (CABG) are at increased risk of perioperative bleeding and morbidity associated with transfusion as a result of acquired and pharmacologically induced impaired platelet function. Settings and Design In this a prospective observational study where 52 patients underwent on-pump CABG were analyzed with ROTEM platelet aggregometry. Materials and Methods Patients were assigned to the “nonexcessive” and “excessive” postoperative bleeding groups according to the postoperative chest tube drainage over 24 hours. Platelet function was assessed by ROTEM platelet using three different activators (arachidonic acid, adenosine diphosphate, and thrombin receptor-activating peptide), at two perioperative time points (T1, before heparinization and T2, 5–10 minutes after protamine administration). Results There were no differences regarding demographic, pre–cardiopulmonary bypass (CPB) platelet count and antiplatelet therapy. Platelet function was impaired over the time course in all parameters with three different activators. At T2 point, area under the curve (AUC) of all the three platelet indices, that is, TRAPTEM, ARATEM, and ADPTEM, showed significant difference between excessive and nonexcessive groups. At both T1 and T2 points, the amplitude after 6 minutes (A6) and maximum slope (MS) parameters of TRAPTEM, ARATEM, and ADPTEM tests were not significantly different in excessive and nonexcessive groups. At T1 point, AUC was also not significantly different in all three ROTEM platelet tests. Results after protamine administration showed correlation with postoperative chest tube drainage. Cut-off values, as determined by receiver operating characteristics (ROC) analyses, had a consistently weak positive predictive value for all tests at T2 time point, whereas negative predictive values were higher. Conclusion Platelet function analysis using ROTEM platelet can help to exclude platelet dysfunction as the reason for bleeding after cardiac surgery. Point-of-care platelet function analysis, particularly in combination with viscoelastic testing can reduce perioperative bleeding and transfusion requirements, as well as improve patient outcomes in cardiac surgery.

Abstract 10572: Efficacy and Safety of Protamine After Catheter Ablation of Atrial Fibrillation: Systematic Review and Meta-Analysis

Introduction: 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. Hypothesis: To determine the efficacy and safety of protamine to expedite vascular hemostasis and ambulation in patients undergoing AF ablation. Methods: Electronic searches on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through June 7, 2021, were performed. The primary outcome was time to ambulate (minutes) and hemostasis (minutes). The secondary outcome was any vascular complications or minor hematoma or cerebrovascular accidents. Results: A total of 5 eligible studies consisting of 637 patients (Protamine group: 515 and no protamine group: 497) were included in the meta-analysis. There was a significant reduction in time to ambulation {mean difference (MD): -176.60, 95% CI -266.87 - -86.32; p< 0.01} and in time to hemostasis between the two groups (MD -13.72, 95% CI -22.01 - -5.44, p<0.01) in the protamine group. There were no differences in the rates of vascular complications (RR 0.46 95% CI 0.17-1.24 for any vascular complication; RR 0.43, 95% CI 0.16-1.2 for minor hematoma) or cerebrovascular accidents (RR 0.62, 95% CI 0.08 - 4.98) between the two groups. Conclusions: 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.

Symptom Status of Patients Undergoing Carotid Endarterectomy in Canada and United States

Previous studies have demonstrated significant geographic variations in the management of carotid artery stenosis despite standard guidelines. To further characterize these practice variations, we assessed differences in patient selection, operative technique, and outcomes for carotid endarterectomy (CEA) in Canada vs. United States. The Vascular Quality Initiative (VQI) was used to identify all patients who underwent CEA between 2010 and 2019 in Canada and United States. Demographic, clinical, and procedural characteristics were recorded and differences between countries were assessed using independent t-test and chi-square test. The primary outcome was the percentage of CEA performed for asymptomatic versus symptomatic disease. The secondary outcomes were 30-day and long-term stroke or death. Associations between country and outcomes were assessed using univariate/multivariate logistic regression and Cox proportional hazards analysis. During the study period, 131,411 US patients and 701 Canadian patients underwent CEA in VQI sites. Patients from the US were older with more comorbidities including hypertension, diabetes, congestive heart failure, and chronic kidney disease. The use of a shunt, patch, drain, or protamine was less common in the US. Most patients had 70 - 99% stenosis, with no difference between regions. The percentage of CEA performed for asymptomatic disease was significantly higher in the US even after adjusting for demographic, clinical, and procedural characteristics (72.4% vs. 30.7%, adjusted OR 3.91 [95% CI 3.21 - 4.78], p < 0.001). Thirty-day stroke/death was low (1.8% vs. 1.9%) and 1-year stroke/death was similar between groups (HR 0.98 [95% CI 0.69 - 1.39], P=0.89). The similarities in 1-year stroke/death persisted in asymptomatic patients (HR 0.70 [95% CI 0.37 - 1.30], P=0.26) and symptomatic patients (HR 1.14 [95% CI 0.74 - 1.73], P=0.56). There are significant variations in CEA practice between Canada and US. In particular, most US patients are treated for asymptomatic disease, whereas most Canadian patients are treated for symptomatic disease. Furthermore, adjunctive procedures including shunting, patch use, and protamine administration are performed less commonly in the US. Despite these differences, perioperative and 1-year stroke/death rates are similar between countries. Future studies should investigate reasons for these variations and quality improvement projects are needed to standardize care.

Dexmedetomidine as an Anaesthetic Adjunct in Patients Undergoing Elective Off-Pump Coronary Artery Bypass Graft Surgery

Background: The aim of the present study was to study the hemodynamic profile of dexmedetomidine during induction and distal anastomosis of coronary arteries in patients undergoing OPCAB in comparison to the institutional practice of using midazolam. Methods: In Group I, (n=25) patients were anaesthetised using fentanyl, pancuronium bromide, Isoflurane and midazolam. Group II (n=25) patients received a loading dose of dexmedetomidine infusion (1µg/Kg) over 10 minutes followed by an infusion of dexmedetomidine at the rate of 0.6 µg/Kg/hour, along with fentanyl, Pancuronium bromide and isoflurane. Heart rate (HR) mean arterial pressure (MAP), pulmonary artery (PA) catheter derived data and BIS were recorded at baseline, at 1 and 3 minutes after induction, at 1, 3 and 5 minutes after intubation, and at 5 and 30 minutes after protamine administration. MAP and HR were recorded every 10 min during the operation, except during distal anastomosis of the coronary arteries when it was recorded every 5 minutes after application of the Octopus tissue stabilising system. Results: The intubation response by way of increase in HR was much less in group II and stabilized by 5 min after intubation. The accompanying hypotension at 1 minute after induction was more in group II, but it was clinically acceptable (81.68±21.74 mm Hg). During distal graft anastomoses HR was in the range of 68 beats/min to 85 beats/min in group II vs. 85 beats/min to 100 beats/min in Group I. The MAP was lower in this group during the distal anastomosis, but it was within clinically acceptable range (&gt; 65 mm Hg). Conclusion: Dexmedetomidine is a viable option as an anaesthetic adjunct in a loading dose of 1µg/Kg followed by an infusion of 0.6 µg/Kg. Future studies will be necessary to show if this provides any outcome benefits.

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

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

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

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

Transit time flow measurement of coronary bypass grafts before and after protamine administration

BackgroundIntraoperative graft assessment with tools like Transit Time Flow Measurement (TTFM) is imperative for quality control in coronary surgery. We investigated the variation of TTFM parameters before and after protamine administration to identify new benchmark parameters for graft quality assessment.MethodsThe database of the REQUEST (“REgistry for QUality AssESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery”) study was retrospectively reviewed. A per graft analysis was performed. Only single grafts (i.e., no sequential nor composite grafts) where both pre- and post-protamine TTFM values were recorded with an acoustical coupling index > 30% were included. Grafts with incomplete data and mixed grafts (arterio-venous) were excluded. A second analysis was performed including single grafts only in the same MAP range pre- and post- protamine administration.ResultsAfter adjusting for MAP, we found a small increase in MGF (29 mL/min to 30 mL/min, p = 0.009) and decrease in PI (2.3 to 2.2, p < 0.001) were observed after the administration of protamine. These changes were especially notable for venous conduits and for CABG procedures performed on-pump.ConclusionThe small changes in TTFM parameters observed before and after protamine administration seem to be clinically irrelevant, despite being statistically significant in aggregate. Our data do not support a need to perform TTFM measurements both before and after protamine administration. A single TTFM measurement taken either before or after protamine may suffice to achieve reliable data on each graft’s performance. Depending on the specific clinical situation and intraoperative changes, more measurements may be informative.Trial registrationClinical Trials Number: NCT02385344, registered February 17th, 2015.

Rotational thromboelastometry and conventional coagulation tests in patients undergoing major cardiac or aortic surgery: a retrospective single-center cohort study

Algorithms for treatment of diffuse bleeding in cardiac surgery are based on intervention thresholds of coagulation tests, such as rotational thromboelastometry (ROTEM) or conventional laboratory tests. The relationship between these two approaches is unclear in patients with increased risk of coagulation abnormalities. We retrospectively analyzed the data of 248 patients undergoing major cardiac and/or aortic surgery. ROTEM and conventional laboratory tests were performed simultaneously after termination of cardiopulmonary bypass and protamine administration to investigate the extrinsic and intrinsic system, and to determine deficiencies in platelets and fibrinogen. We evaluated the association between ROTEM and conventional tests by linear regression analysis and compared the frequency of exceeding established thresholds for clinical intervention. Significant linear associations between ROTEM 10 min after the start of coagulation, and plasma fibrinogen concentration or platelet count (FIBTEM A10, R2 = 0.67, p < 0.001; EXTEM A10, R2 = 0.47, p < 0.001) were obtained. However, the 95% prediction intervals exceeded clinically useful ranges (92–233 mg/dL fibrinogen at the intervention threshold of FIBTEM A10 = 10 mm; 14 × 103–122 × 103/µL platelets at the intervention threshold of EXTEM A10 = 40 mm). The association between EXTEM and INR (R2 = 0.23), and INTEM and aPTT (R2 = 0.095) was poor. The frequency of exceeding intervention thresholds and, consequently, of triggering treatment, varied markedly between ROTEM and conventional tests (p < 0.001 for all comparisons). The predictability of conventional coagulation test results by ROTEM is limited, thus hampering the interchangeability of methods in clinical practice.

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

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. 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). 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. ClinicalTrials.gov Unique identifier NCT03532594.

Effect of Lidocaine Pre-Treatment on Protamine-Induced Pulmonary Vascular Reaction During the Repair of Congenital Heart Disease.

BackgroundProtamine is a polycationic, and a strong basic peptide isolated from Clupeidae or Salmonidae fishes’ sperm, which is rich in arginine and highly alkaline.ObjectiveTo explore the effect of lidocaine pre-treatment on protamine-induced pulmonary vascular reaction during the repair of congenital heart disease.MethodsEighty patients undergoing repair of congenital heart disease were randomly divided into four groups: A1 (non-pulmonary hypertension + lidocaine pre-treatment) group, A2 (non-pulmonary hypertension + normal saline) group, B1 (pulmonary hypertension + lidocaine pre-treatment) group, and B2 (pulmonary hypertension + normal saline) group. Hemodynamic parameters, pulmonary inflammation, and pulmonary function were assessed at six intraoperative time points, two intraoperative time points and three intraoperative time points, respectively. P-value <0.05 was considered statistically significant.ResultsA2 group exhibited increased PAP, Paw, RI and A-aDO2. B2 group exhibited increased Paw, RI and A-aDO2 and decreased Cydn and OI after protamine administration. These changes were not observed in A1 and B1 group. Compared with A1 and B1 groups, plasma TXB2 level in A2 and B2 group was higher, but 6-keto-PGF1a in A2 and B2 groups was lower. Incidence of protamine adverse reactions in A1 and B1 group was lower than that in A2 and B2 group.ConclusionPrecondition of lidocaine before neutralization of heparin may be effective for protamine-induced pulmonary vascular reaction during CHD repair.

Simple periprocedural precautions to reduce Doppler microembolic signals during AF ablation

BackgroundDoppler microembolic signals (MES) occur during atrial fibrillation ablation despite of permanent flushed transseptal sheaths, frequent controls of periprocedural coagulation status and the use of irrigated ablation cathetersPurposeTo investigate the number and type of MES depending on the procedure time, prespecified procedure steps, the activated clotting time (ACT) during the ablation procedure and the catheter contact force.MethodsIn a prospective trial, 53 consecutive atrial fibrillation patients underwent pulmonary vein isolation by super-irrigated “point-by-point” ablation. All patients underwent a periinterventional, continuous transcranial Doppler examination (TCD) of the bilateral middle cerebral arteries during the complete ablation procedure.ResultsAn average of 686±226 microembolic signals were detected by permanent transcranial Doppler. Thereby, 569±208 signals were differentiated as gaseous and 117±31 as solid MES. The number of MES with regard to defined procedure steps were as follows: gaseous: [transseptal puncture, 26 ± 28; sheath flushing, 24±12; catheter change, 21±11; angiography, 101±28; mapping, 9±9; ablation, 439±192; protamine administration, 0±0]; solid: [transseptal puncture, 8±8; sheath flushing, 9±5; catheter replacement, 6±6; angiography, not measurable; mapping, 2±5; ablation, 41±22; protamine administration, 0±0]. Significantly less MES occurred with shorter procedure time, higher ACT and the use of tissue contact force monitoring.ConclusionThe current study demonstrates that during atrial fibrillation ablation using irrigated, “point-by-point” RF ablation, masses of microembolic signals are detected in transcranial ultrasound especially in the period of RF current application. The number of MES depends on the total procedure time and the reached ACT during ablation. The use of contact force monitoring might reduce MES during RF ablation.

Antithrombotic Therapy in Chronic Total Occlusion Interventions

Chronic total occlusion (CTO) recanalization is among the most complex subsets of coronary interventions. Hence, optimum peri- and post-procedural anticoagulation and antiplatelet therapy is key for the achievement of successful revascularization and reduction of major adverse cardiovascular outcomes in patients undergoing CTO percutaneous coronary intervention (PCI). Unfractionated heparin is still considered the gold standard anticoagulant because its action can be reversed by protamine administration, with bivalirudin being reserved mainly for patients with heparin-induced thrombocytopenia. However, small studies comparing unfractionated heparin with bivalirudin in CTO interventions have shown similar outcomes. Glycoprotein IIb/IIIa inhibitors should, in general, be avoided. Aspirin in combination with clopidogrel for 6–12 months is the standard post CTO PCI dual antiplatelet regimen. For the most complex cases, clopidogrel can be substituted by a more potent P2Y12 inhibitor, namely ticagrelor or prasugrel.

Imaging the dynamics and microstructure of fibrin clot polymerization in cardiac surgical patients using spectrally encoded confocal microscopy.

During cardiac surgery with cardiopulmonary bypass (CPB), altered hemostatic balance may disrupt fibrin assembly, predisposing patients to perioperative hemorrhage. We investigated the utility of a novel device termed spectrally-encoded confocal microscopy (SECM) for assessing fibrin clot polymerization following heparin and protamine administration in CPB patients. SECM is a novel, high-speed optical approach to visualize and quantify fibrin clot formation in three dimensions with high spatial resolution (1.0μm) over a volumetric field-of-view (165 × 4000 × 36 μm). The measurement sensitivity of SECM was first determined using plasma samples from normal subjects spiked with heparin and protamine. Next, SECM was performed in plasma samples from patients on CPB to quantify the extent to which fibrin clot dynamics and microstructure were altered by CPB exposure. In spiked samples, prolonged fibrin time (4.4 ± 1.8 to 49.3 ± 16.8min, p < 0.001) and diminished fibrin network density (0.079 ± 0.010 to 0.001 ± 0.002 A.U, p < 0.001) with increasing heparin concentration were reported by SECM. Furthermore, fibrin network density was not restored to baseline levels in protamine-treated samples. In CPB patients, SECM reported lower fibrin network density in protaminized samples (0.055 ± 0.01 A.U. [Arbitrary units]) vs baseline values (0.066 ± 0.009 A.U.) (p=0.03) despite comparable fibrin time (baseline=6.0 ± 1.3, protamine=6.4 ± 1.6min, p=0.5). In these patients, additional metrics including fibrin heterogeneity, length and straightness were quantified. Note, SECM revealed that following protamine administration with CPB exposure, fibrin clots were more heterogeneous (baseline=0.11 ± 0.02 A.U, protamine=0.08 ± 0.01 A.U, p=0.008) with straighter fibers (baseline=0.918 ± 0.003A.U, protamine=0.928 ± 0.0006A.U. p < 0.001). By providing the capability to rapidly visualize and quantify fibrin clot microstructure, SECM could furnish a new approach for assessing clot stability and hemostasis in cardiac surgical patients.

Large cardiac wall hematoma with rapid growth: a case report of a potentially catastrophic complication during cardiac surgery

BackgroundRapid growth of cardiac wall hematoma is a rare but potentially fatal complication of cardiac surgery. However, its pathophysiology and optimal management remain undefined.Case presentationHere we present a rare case of a large cardiac wall hematoma in the right ventricle during a thoracic aortic and valvular surgery. The hematoma expanded rapidly with epicardial rupture during cardiopulmonary bypass. We could establish non-surgical hemostasis and prevent further expansion of hematoma by early weaning of the cardiopulmonary bypass, followed by the administration of protamine and manual compression by hemostatic agent application. His postoperative recovery was uneventful and upon computed tomography analysis, the hematoma was observed to have absorbed completely at 1 week postoperatively. The patient is doing well 1 year after the surgery without evidence of recurrent cardiac wall hematoma on follow-up computed tomography.ConclusionsCardiovascular surgeons should bear in mind this potentially catastrophic complication during cardiac surgery. Because of the vulnerability of the cardiac wall at the area of the hematoma, we believe that a hemostatic approach without sutures may be effective for this lethal complication.

Less is more: We are administering too much protamine in cardiac surgery.

Context:Protamine is routinely administered to neutralize the anticlotting effects of heparin, traditionally at a dose of 1 mg for every 100 IU of heparin—a 1:1 ratio protamine sparing effects—but this is based more on experience and practice than literature evidence. The use of Hemostasis Management System (HMS) allows an individualized heparin and protamine titration. This usually results in a decreased protamine dose, thus limiting its side effects, including paradox anticoagulation.Aims:This study aims to assess how the use of HMS allows to reduction of protamine administration while restoring the basal activated clotting time (ACT) at the end of cardiac surgery.Settings and Design:A retrospective observational study in a tertiary care university hospital.Subjects and Methods:We analyzed data from 42 consecutive patients undergoing cardiopulmonary bypass (CPB) for cardiac surgery. For all patients HMS tests were performed before and after CPB, to determine how much heparin was needed to reach target ACT, and how much protamine was needed to reverse it.Results:At the end of cardiopulmonary bypass, 2.2 ± 0.5 mg/kg of protamine was sufficient to reverse heparin effects. The protamine-to-heparin ratio was 0.56:1 over heparin total dose (a 44% reduction) and 0.84:1 over heparin initial dose (a 16% reduction).Conclusion:A lower dose of protamine was sufficient to revert heparin effects after cardiopulmonary bypass. While larger studies are needed to confirm these findings and detect differences in clinically relevant outcomes, the administration of a lower protamine dose is endorsed by current guidelines and may help to avoid the detrimental effects of protamine overdose, including paradox bleeding.

Excessive oozing through the fabric of the branched Cryolife-Jotec Evita Open NEO hybrid prosthesis

We report 3 cases of excessive oozing after aortic arch replacement using the frozen elephant trunk technique through the fabric of the branched Cryolife-Jotec Evita Open NEO hybrid prosthesis. After weaning from cardiopulmonary bypass, protamine administration as well as standard substitution of plasmatic and cellular coagulation adjusted to thrombelastometry, excessive oozing persisted leading to a complicated postoperative course in all 3 patients.

Thromboelastography During Rewarming for Management of Pediatric Cardiac Surgery Patients

BackgroundThromboelastography (TEG) predicts bleeding in pediatric patients undergoing cardiac surgical procedure. We hypothesize that TEG indicators at rewarming correlate with postprotamine values and that rewarming TEG is associated with surrogate end points for postoperative bleeding in pediatric patients undergoing complex cardiac surgical procedure. MethodsIn a retrospective study of 703 pediatric (≤18 years) patients undergoing complex cardiac surgical procedures, TEG results obtained during rewarming and after protamine administration were compared using linear regression. A composite end point of extended blood product transfusion or surgical reexploration for bleeding was used as a surrogate for postoperative bleeding. ResultsBy multivariable analysis, longer cardiopulmonary bypass time and lower TEG maximal amplitude (MA) during rewarming were independently associated with the risk of the composite end point in the operating room or in the intensive care unit (P < .05). Among patients with an MA of less than 45 mm during rewarming, those who received a platelet transfusion in the operating room compared with those who did not were less likely to reach the composite end point within the subsequent 24 hours (8% vs 32%, respectively; P < .01). Good correlation was observed between TEG variables at rewarming vs after protamine administration (Pearson r ≥ 0.7). The relationship between platelet transfusion volume (mL/kg) and the percentage change in the MA was determined using linear regression, and a platelet transfusion calculator was generated. ConclusionsA lower MA during rewarming is associated with an increased risk of perioperative bleeding. In patients with a rewarming MA of less than 45 mm, an intraoperative platelet transfusion may reduce the risk of subsequent bleeding. Individualized platelet transfusion therapy based on rewarming TEG may reduce the risk of bleeding while minimizing unnecessary platelet transfusion.

Effects of Modified Ultrafiltration on Thromboelastographic Profile after Pediatric Cardiac Surgery

Modified ultrafiltration (MUF) is still used after pediatric cardiopulmonary bypass (CPB) in some pediatric cardiac surgery centers to decrease transfusion requirements. Other potential benefits of MUF include clearance of inflammatory markers and improvement in myocardial function. Our hypothesis is that MUF will hemoconcentrate coagulation factors and improve thromboelastography (TEG) parameters after pediatric CPB. Patients younger than 6 months were prospectively enrolled over a year. TEG was carried out before MUF, after MUF, and after protamine administration. Paired t tests were conducted to compare values pre-MUF and post-MUF as well as post-MUF and post-protamine administration. Thirty patients were enrolled in the study, with 20 (67%) neonates in the cohort. Seven arterial switch operations and nine Norwood procedures were found to be performed among the cohort. Reaction time (R), angle (α), and maximum amplitude (MA) were significantly worse post-MUF compared with pre-MUF (p &lt; .001). They improved significantly after protamine administration compared with post-MUF (p &lt; .001). The amount of fluid removal was significantly associated with a worse post-MUF R, angle, and MA and worse post-protamine administration, angle, and MA but with no effect on post-protamine R. MUF caused worsening of TEG parameters that is reversed by protamine administration.

Effects of Modified Ultrafiltration on Thromboelastographic Profile after Pediatric Cardiac Surgery.

Modified ultrafiltration (MUF) is still used after pediatric cardiopulmonary bypass (CPB) in some pediatric cardiac surgery centers to decrease transfusion requirements. Other potential benefits of MUF include clearance of inflammatory markers and improvement in myocardial function. Our hypothesis is that MUF will hemoconcentrate coagulation factors and improve thromboelastography (TEG) parameters after pediatric CPB. Patients younger than 6 months were prospectively enrolled over a year. TEG was carried out before MUF, after MUF, and after protamine administration. Paired t tests were conducted to compare values pre-MUF and post-MUF as well as post-MUF and post-protamine administration. Thirty patients were enrolled in the study, with 20 (67%) neonates in the cohort. Seven arterial switch operations and nine Norwood procedures were found to be performed among the cohort. Reaction time (R), angle (α), and maximum amplitude (MA) were significantly worse post-MUF compared with pre-MUF (p < .001). They improved significantly after protamine administration compared with post-MUF (p < .001). The amount of fluid removal was significantly associated with a worse post-MUF R, angle, and MA and worse post-protamine administration, angle, and MA but with no effect on post-protamine R. MUF caused worsening of TEG parameters that is reversed by protamine administration.

Point-of-Care Measurement of Kaolin Activated Clotting Time during Cardiopulmonary Bypass: A Single Sample Comparison between ACT Plus and i-STAT.

Heparin anticoagulation monitoring by point-of-care activated clotting time (ACT) is essential for cardiopulmonary bypass (CPB) initiation, maintenance, and anticoagulant reversal. Concerns exist regarding the comparability of kaolin activated ACT devices. The current study, therefore, evaluated the agreement of ACT assays using parallel measurements performed on two commonly used devices. Measurements were conducted in a split-sample fashion on both the ACT Plus (Medtronic, Minneapolis, MN) and i-STAT (Abbott Point of Care, Princeton, NJ) analyzers. Blood samples from 100 adult patients undergoing elective cardiac surgery with CPB were assayed at specified time points: before heparinization, following systemic heparinization, after CPB initiation, every 30 minutes during CPB, and following protamine administration. A cutoff value of 400 seconds (s) was used as part of the local protocol. Measurements were compared using t tests or Wilcoxon signed-rank tests, linear regression, and Bland-Altman analyses. Parallel ACT measurements demonstrated a good linear correlation (r = .831, p < .001). The overall median difference between both measurements was significantly different from zero, amounting to 87 (14-189) (p < .001), with limits of agreement of -124 and 333s. The i-STAT-derived ACT values were systematically lower than the ACT Plus values, which was more pronounced during CPB. Fourteen patients received additional heparin during CPB at a median ACT Plus value of 414s, with a concomitant median i-STAT value of 316s. Assuming 308s as the theoretical i-STAT cutoff value based on the linear regression equation and an ACT Plus threshold of 400s, 29 patients would have received additional heparin. Based on these results, kaolin point-of-care ACT devices cannot be used interchangeably. Device-specific predefined target values are warranted to avert heparin overdosing during CPB.