The FIBTEM paradox: Do coronary artery bypass grafting patients with high baseline FIBTEM clot firmness need more allogeneic blood transfusion?

BACKGROUND: Fibrinogen thromboelastometry (FIBTEM) test is clinically used for rotational thromboelastometry as a surrogate measure of fibrinogen. Elevated fibrinogen might confer protection against bleeding after major surgery. This single-center study was conducted to assess any relationship between baseline FIBTEM value and exposure to allogeneic transfusion in patients undergoing coronary artery bypass grafting (CABG). STUDY DESIGN AND METHODS: Data were obtained retrospectively from local FIBTEM data and the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database between 2016 and 2019. Preoperative FIBTEM 10-min amplitude (A10) was categorized as low (≤ 18 mm), intermediate (19-23 mm), or high (≥24 mm). The primary outcome was any transfusion during the hospitalization, including red blood cells (RBCs), platelets, plasma, and cryoprecipitate. A multivariable regression model was used to adjust for confounders and calculate an odds ratio (OR) for any transfusion. RESULTS: The high FIBTEM group included more female and African-American patients, as well as urgent surgery. The STS predicted risks of morbidity and mortality were greater, and anemia was most prevalent with high FIBTEM. Unadjusted blood transfusion rates were increased with high FIBTEM due to RBC transfusion, but non-RBC transfusion was highest with low FIBTEM. After adjustments, a lower OR for transfusion was associated with high FIBTEM (0.426; 95% confidence interval, 0.199-0.914) compared to low FIBTEM. CONCLUSION: The high FIBTEM group frequently presented with anemia and comorbidities, and received more RBCs but not non-RBC products. Postoperative blood loss was less with high FIBTEM, and after adjustments, it conferred protection against any transfusion.

In vitro effects of emicizumab on activated clotting time in blood samples from cardiac surgical patients.

BACKGROUND: Heparin management in hemophilia A (HA) patients with a factor VIII (FVIII) inhibitor can be challenging due to severe activated clotting time (ACT) prolongations. It is important to better understand the impact of emicizumab, a FVIII mimetic on ACT, and tissue factor (TF)-based coagulation assays. METHODS: Whole blood from 18 patients undergoing cardiopulmonary bypass (CPB) were mixed in vitro with pooled normal plasma, FVIII-deficient or FVIII-inhibitor plasma to affect functional FVIII levels. ACTs and heparin concentration by protamine titration were measured in whole blood mixture with/without emicizumab (50-100 µg/ml). Thrombin generation and plasmin generation were measured in the patient's plasma mixed with normal plasma or FVIII-inhibitor plasma to assess the impact of emicizumab under low TF activation. RESULTS: FVIII inhibitors prolonged ACTs by 2.2-fold compared to those in normal plasma mixture at baseline. During CPB, ACTs in normal plasma mixture, and FVIII-deficient mixture were in 400s, but ACTs reached 900s in FVIII-inhibitor mixture. Emicizumab shortened ACTs by up to 100s in normal plasma mixture, and FVIII-deficient mixtures. ACTs remained over 600s in FVIII-inhibitor mixture, despite adding emicizumab at 100 µg/ml. Heparin concentration measured by TF-based protamine titration was unaffected. Emicizumab enhanced thrombin peak in the presence of FVIII inhibitors, whereas plasmin generation was mainly affected by thrombin generation, and systemic use of ɛ-aminocaproic acid. CONCLUSIONS: FVIII inhibitors extensively prolong ACTs in heparinized whole blood, and clinical levels of emicizumab partially reverse ACT values. Protamine titration should be considered for optimal heparin monitoring in emicizumab-treated patients with FVIII inhibitors.

Long time behavior and stable patterns in high-dimensional polarity models of asymmetric cell division.

Asymmetric cell division is one of the fundamental processes to create cell diversity in the early stage of embryonic development. During this process, the polarity formation in the cell membrane has been considered as a key process by which the entire polarity formation in the cytosol is controlled, and it has been extensively studied in both experiments and mathematical models. Nonetheless, a mathematically rigorous analysis of the polarity formation in the asymmetric cell division has been little explored, particularly for bulk-surface models. In this article, we deal with polarity models proposed for describing the PAR polarity formation in the asymmetric cell division of a C. elegans embryo. Using a simpler but mathematically consistent model, we exhibit the long time behavior of the polarity formation of a bulk-surface cell. Moreover, we mathematically prove the existence of stable polarity solutions of the model equation in an arbitrary high-dimensional domain and analyse how the boundary position of polarity domain is determined. Our results propose that the existence and dynamics of the polarity in the asymmetric cell division can be understood universally in terms of basic mathematical structures.

TEE image quality improvement with our devised probe cover.

OBJECTIVE(S): Our hypothesis was that our devised transesophageal echocardiography probe cover with the capacity for pinpoint suction would improve image quality. DESIGN: Prospective cohort study. SETTING: Single tertiary medical center. PARTICIPANTS: Patients undergoing surgery requiring intraoperative transesophageal echocardiography. INTERVENTIONS: Suctioning with inserted orogastric tube. MEASUREMENTS AND MAIN RESULTS: Changes in image quality with suctioning were assessed by 2 methods. In method #1, investigators categorized the quality of all acquired images on a numeric scale based on each investigator's impression (1: very poor, 2: poor, 3: acceptable, 4: good, and 5: very good). In method #2, the reproducibility of the left ventricular fraction area change (LV FAC) was assessed, assuming that improved transgastric midpapillary short-axis view image quality would yield better LV FAC reproducibility. With method #1, for midesophageal views, 26.5%, 70.5%, and 3.0% of images showed improved, the same, and worsened image quality, respectively. For transgastric views, 55.3%, 43.3%, and 1.4% showed improved, the same, and worsened image quality, respectively. For deep transgastric views, 60.0%, 38.0%, and 2.0% showed improved, the same, and worsened image quality, respectively. With method #2, the presuction group had an ICC of 0.942 (95% CI: 0.91, 0.965). The postsuction group had an ICC of 0.988 (95% CI: 0.981, 0.993). CONCLUSIONS: Our investigation validates the potential image quality improvement withour devised TEE probe cover. However, its clinical validity needs to be confirmed by further studies.

Hepatic Vein Flow Index During Orthotopic Liver Transplantation as a Predictive Factor for Postoperative Early Allograft Dysfunction.

OBJECTIVES: The authors devised a hepatic vein flow index (HVFi), using intraoperative transesophageal echocardiography and graft weight, and investigated its predictive value for postoperative graft function in orthotopic liver transplant. DESIGN: Prospective clinical trial. SETTING,: Single-center tertiary academic hospital. PARTICIPANTS: Ninety-seven patients who had orthotopic liver transplant with the piggy-back technique between February 2018 and December 2019. MEASUREMENTS AND MAIN RESULTS: HVFi was defined with HV flow/graft weight. Patients who developed early graft dysfunction (EAD) had low HVFi in systole (HVFi sys, 1.23 v 2.19 L/min/kg, p < 0.01), low HVFi in diastole (HVFi dia, 0.87 v 1.54 L/min/kg, p < 0.01), low hepatic vein flow (HVF) in systole (HVF sys, 2.04 v 3.95 L/min, p < 0.01), and low HVF in diastole (HVF dia, 1.44 v 2.63 L/min, p < 0.01). More cardiac death, more vasopressors at the time of measurement, more acute rejection, longer time to normalize total bilirubin (TIME t-bil), longer surgery time, longer neohepatic time, and more packed red blood cell transfusion were observed in the EAD patients. All HVF parameters were negatively correlated with TIME t-bil (HVFi sys R = -0.406, p < 0.01; HFVi dia R = -0.442, p < 0.01; HVF sys R = -0.44, p < 0.01; HVF dia R = -0.467, p < 0.01). The receiver operating characteristic curve analysis determined the best cut-off levels of HVFi to predict occurrence of EAD (HVFi sys <1.608, HVFi dia <0.784 L/min/kg), acute rejection (HVFi sys <1.388, HVFi dia <1.077 L/min/kg), and prolonged high total bilirubin (HVFi sys <1.471, HVFi dia <1.087 L/min/kg). CONCLUSIONS: The authors' devised HVFi has the potential to predict the postoperative graft function.

Perioperative Management of Patients With Hereditary Angioedema With Special Considerations for Cardiopulmonary Bypass.

Hereditary angioedema (HAE) is a rare autosomal dominant disorder mostly due to the deficiency of C1-esterase inhibitor (C1-INH). Reduced C1-INH activity below ~38% disrupts homeostasis of bradykinin (BK) formation by increasing kallikrein activation and causes recurrent angioedema attacks affecting the face, extremities, genitals, bowels, oropharynx, and larynx. HAE symptoms can be debilitating and potentially life-threatening. The recent clinical developments of biological and pharmacological agents have immensely improved acute and long-term care of patients with moderate-to-severe HAE. The therapies are given as on-demand and/or prophylaxis, and self-administration is highly recommended and performed with some agents via intravenous or subcutaneous route. Perioperative clinicians need to be familiar with the symptoms and diagnosis of HAE as well as available therapies because of the potential need for airway management, sedation, or anesthesia for various medical and surgical procedures and postoperative care. Cardiovascular surgery using cardiopulmonary bypass is a unique condition in which heparinized blood comes into direct contact with an artificial surface while pulmonary circulation, a major reserve of angiotensin-converting enzyme (ACE), becomes excluded. These changes result in systemic kallikrein activation and BK formation even in non-HAE patients. The objectives of this review are (1) to review pathophysiology of HAE and laboratory testing, (2) to summarize pertinent pharmacological data on the prophylactic and on-demand treatment strategies, and (3) to discuss available clinical data for perioperative management in cardiovascular surgery.

A laser mount probe holder facilitates fixation of the optimized ultrasound image and needle alignment in-plane to the ultrasound beam during ultrasound-guided peripheral nerve block.

Laser guidance facilitates needle alignment in-plane to the ultrasound beam. Once the ultrasound image is optimized, there is no further need to maneuver the probe. Therefore, we designed a laser mount probe holder prototype, and examined the ease of visualization of the needle tip using the laser mount probe holder. The needle brightness was quantitatively measured using an image analysis software. We found that the laser mount probe holder is useful, not only to visualize the needle tip in the ultrasound plane, but also to fix the best ultrasound image.

Modified Tricuspid Annular Plane Systolic Excursion Using Transesophageal Echocardiography and Its Utility to Predict Postoperative Course in Heart Transplantation and Left Ventricular Assist Device Implantation.

OBJECTIVES: Perioperative right ventricular (RV) function is important for determining the postoperative course in heart transplantation (HT) and left ventricular assist device (LVAD) implantation. The authors describe a modified tricuspid annular plane systolic excursion (m-TAPSE) using transesophageal echocardiography and assessed its clinical utility in HT and LVAD. DESIGN: Retrospective medical record review. SETTING: A single tertiary-care medical center. PARTICIPANTS: Forty-eight patients who underwent successful HT and 80 patients who underwent successful LVAD placement. MEASUREMENTS AND MAIN RESULTS: Statistically significant correlation between m-TAPSE and RV fractional area change (FAC) was seen for HT and LVAD (r = 0.462, p < 0.01 and r = 0.597, p < 0.01, respectively). For HT, receiver operating characteristics curve analysis yielded that m-TAPSE <0.64 cm provides 100% specificity and 57.1% sensitivity in predicting postoperative nitric oxide (NO) use, whereas RV FAC <24.1% provides 95.1% specificity and 71.4% sensitivity in predicting postoperative NO use (area under the curve 0.798 [95% confidence interval (CI), 0.595-1] v 0.826 [95% CI, 0.581-1], p = 0.397). For LVAD, m-TAPSE <0.71 cm provides 66.7% specificity and 87.5% sensitivity in predicting postoperative NO use, whereas RV FAC <16.3% provides 79.4% specificity and 62.5% sensitivity in predicting postoperative NO use (area under the curve 0.829 [95% CI, 0.732-0.927] v 0.691 [95% CI, 0.54-0.842], p < 0.05). CONCLUSIONS: m-TAPSE validated a good correlation to RV systolic function as reflected by RV FAC for both HT and LVAD. For HT, m-TAPSE was helpful for predicting postoperative NO use; whereas for LVAD, m-TAPSE was helpful for predicting postoperative NO use and RV assist device implantation. m-TAPSE should be considered as a useful parameter to decide postoperative management for these cases.

Modified Tricuspid Annular Plane Systolic Excursion Using Transesophageal Echocardiography for Assessment of Right Ventricular Function.

OBJECTIVES: The authors defined a modified tricuspid annular plane systolic excursion (m-TAPSE) measurement using the transesophageal echocardiography (TEE) midesophogeal 4-chamber view and investigated its clinical validity in comparison with other indices of heart function. DESIGN: Retrospective medical record review. SETTING: A single tertiary care medical center. PARTICIPANTS: One hundred ninety-six patients who underwent successful mitral valve repair. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were divided into 2 groups using a proposed guideline cutoff of 16 mm of m-TAPSE. m-TAPSE was measured by apical systolic/diastolic shortening as shown in the TEE midesophogeal 4-chamber view. Right ventricular fractional area change (RV FAC) was measured by using planimetry in the same view. Correlation analysis was performed for m-TAPSE and RV FAC. One hundred six (54.1%) patients showed m-TAPSE>16 mm and 90 patients (45.9%) showed m-TAPSE<16 mm. There were no significant differences in patient demographics and comorbidities between the 2 groups except for atrial fibrillation (7.5% in m-TAPSE>16 mm v 24.4% in m-TAPSE<16 mm, p<0.001). Compared to the m-TAPSE>16 mm group, the m-TAPSE<16 mm group demonstrated significantly lower RV FAC (38.0±10.4 v 26.4±8.1, p<0.001). The correlation coefficient between m-TAPSE and RV FAC was 0.618, p< 0.001. CONCLUSIONS: m-TAPSE validated a good correlation to right ventricular systolic function as reflected by RV FAC. m-TAPSE should be considered as an easily measurable parameter to evaluate right ventricular systolic function.

[A Trained-in-Japan Anesthesiologist Going Through Anesthesia Training in the United States : What Adjustments Should be Made for Upcoming Renewal in Anesthesia Board Certification in Japan?].

We reviewed the anesthesiology training in the United States from the viewpoint of Japanese Anes- thesiologists. The Accreditation Council for Graduate Medical Education (ACGME) strictly supervises anes- thesiology residency programs in the U.S. Recently, the ACGME has become stricter on training supervi- sion, and American Board of Anesthesiology (ABA) revised its board examination system. The quality of anesthesia training in the U. S., how- ever, is decreasing because of new regulations. Addi- tionally, in the continuing economic recession, hospitals have started to hire more nurse anesthetists (CRNA) with cheaper salary than anesthesiologists. This situa- tion led more anesthesiology residents to seek an extra year of subspecialty fellowship training and research experience. This trend will come to Japan in the near future, for which we should be well prepared. As the first step, the process for Japanese Anesthesiology Board Recertification should be modified. Continuing medical education should be mandatory for each re- newal with recertification examination. Second, the number of residents and the quality of each program should be strictly supervised by a third party. Lastly, we should encourage residents to seek subspecialty training and more research experience to become bet- ter anesthesiologists.

[Diagnosis and evaluation of a patient with cor triatriatum using perioperative transesophageal echocardiography].

Cor triatriatum is a rare congenital cardiac anomaly accounting for only 0.1-0.4% of all congenital heart diseases usually diagnosed in infancy or childhood and rarely found in adults. It is characterized by fibromuscular membrane dividing the left atrium into two chambers. This congenital heart disease is reported to be frequently associated with variety of cardiac anomalies such as an atrial septal defect, anomalous pulmonary venous drainage, and persistent left superior vena cava. A woman with no cardiac history was admitted to the hospital due to acute heart failure and diagnosed as severe mitral regurgitation and cor triatriatum by pre-orerative transthoracic echocardiography. Emergency mitral valve plasty was undertaken because of the severity of mitral regurgitation without determining the detailed type of cor triatriatum. Thus, diagnosis of the type of cor triatriatum with perioperative transesophageal echocardiography (TEE) was required to establish correct cardiopulmonary bypass and determine the operative procedure. Perioperative TEE revealed that the type was Lucas-Schmidt- I A, and cardiopulmonary bypass was established safely. Operation was performed without any problems. The TEE skill of our anesthesiologists could contribute to the safe management of the cardiac surgery.

No Association of Early Postoperative Heart Rate With Outcomes After Coronary Artery Bypass Grafting.

BACKGROUND: Elevated perioperative heart rate potentially causes perioperative myocardial injury because of imbalance in oxygen supply and demand. However, large multicenter studies evaluating early postoperative heart rate and major adverse cardiac and cerebrovascular events (MACCEs) are lacking. OBJECTIVE: To assess the associations of 4 postoperative heart rate assessment methods with in-hospital MACCEs after elective coronary artery bypass grafting (CABG). METHODS: Using data from the eICU Collaborative Research Database in the United States from 2014 to 2015, the study evaluated postoperative heart rate measured during hospitalization within 24 hours after intensive care unit admission. Four heart rate assessment methods were evaluated: maximum heart rate, duration above heart rate 100/min, area above heart rate 100/min, and time-weighted average heart rate. The outcome was in-hospital MACCEs, defined as a composite of in-hospital death, myocardial infarction, angina, arrhythmia, heart failure, stroke, cardiac arrest, or repeat revascularization. RESULTS: Among 2585 patients, the crude rate of in-hospital MACCEs was 6.2%. In multivariable logistic regression analysis, the adjusted odds ratios (95% CI) for in-hospital MAC-CEs assessed by maximum heart rate in each heart rate category (beats per minute: >100-110, >110-120, >120-130, and >130) were 1.43 (0.95-2.15), 0.98 (0.56-1.64), 1.47 (0.76-2.69), and 1.71 (0.80-3.35), respectively. Similarly, none of the other 3 methods were associated with MACCEs. CONCLUSIONS: More research is needed to assess the usefulness of heart rate measurement in patients after CABG.

Immediate Postoperative Extubation Decreases Pulmonary Complications in Liver Transplant Patients.

BACKGROUND: Fast-track anesthesia in liver transplantation (LT) has been discussed over the past few decades; however, factors associated with immediate extubation after LT surgery are not well defined. This study aimed to identify predictive factors and examine impacts of immediate extubation on post-LT outcomes. METHODS: A total of 279 LT patients between January 2014 and May 2017 were included. Primary outcome was immediate extubation after LT. Other postoperative outcomes included reintubation, intensive care unit stay and cost, pulmonary complications within 90 days, and 90-day graft survival. Logistic regression was performed to identify factors that were predictive for immediate extubation. A matched control was used to study immediate extubation effect on the other postoperative outcomes. RESULTS: Of these 279 patients, 80 (28.7%) underwent immediate extubation. Patients with anhepatic time >75 minutes and with total intraoperative blood transfusion ≥12 units were less likely to be immediately extubated (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.89; P = 0.02; OR, 0.11; 95% CI, 0.05-0.21; P < 0.001). The multivariable analysis showed immediate extubation significantly decreased the risk of pulmonary complications (OR, 0.34; 95% CI, 0.15-0.77; P = 0.01). According to a matched case-control model (immediate group [n = 72], delayed group [n = 72]), the immediate group had a significantly lower rate of pulmonary complications (11.1% versus 27.8%; P = 0.012). Intensive care unit stay and cost were relatively lower in the immediate group (2 versus 3 d; P = 0.082; $5700 versus $7710; P = 0.11). Reintubation rates (2.8% versus 2.8%; P > 0.9) and 90-day graft survival rates (95.8% versus 98.6%; P = 0.31) were similar. CONCLUSIONS: Immediate extubation post-LT in appropriate patients is safe and may improve patient outcomes and resource allocation.

Efficacy of amiodarone on refractory ventricular fibrillation resistant to lidocaine and cardioversion during weaning from cardiopulmonary bypass in aortic valve replacement for severe aortic stenosis with left ventricular hypertrophy.

Intravenous injection of amiodarone, a class III anti-arrhythmic is widely used for persistent refractory arrhythmias. We present a case report suggesting the efficacy of amiodarone in refractory ventricular fibrillation (Vf) during weaning from cardiopulmonary bypass (CPB). A 66-year-old woman with hypertension had a medical examination as a result of an episode of palpitations and syncope. Echocardiography and an invasive hemodynamic study revealed severe aortic stenosis (AS) with left ventricular (LV) hypertrophy because of calcified degeneration in a congenital bicuspid aortic valve (AV). Aortic valve replacement (AVR) was scheduled under general anesthesia and CPB. Intraoperative diagnosis was AS with calcified AV, LV hypertrophy, and aneurysm of ascending aorta (Ao). AVR with a biological valve, artificial vessel replacement of ascending Ao, and excision of the outflow myocardial septum were performed under CPB with intermittent antegrade blood cardioplegia at a body temperature (BT) of 24°C. The patient suffered from Vf at a BT of 35.3°C. Vf was not responsive to lidocaine 100 mg and 10 direct current (DC) shocks. After continuous intravenous infusion of amiodarone 225 mg/h for 10 min and a single intravenous injection of amiodarone 150 mg followed by a single DC shock, she returned to normal sinus rhythm. Sinus rhythm was maintained by continuous intravenous infusion of amiodarone 60 mg/h. Total CPB time was 5 h 43 min. Aortic cross-clamping time was 3 h 50 min. Administration of amiodarone is effective for refractory Vf resistant to lidocaine and cardioversion during weaning from CPB in cardiac surgery for heart diseases with LV hypertrophy.

Inhaled Pulmonary Vasodilators and Thoracic Organ Transplantation: Does Evidence Support Its Use and Cost Benefit?

In heart transplantation, pulmonary hypertension and increased pulmonary vascular resistance followed by donor right ventricular dysfunction remain a major cause of perioperative morbidity and mortality. In lung transplantation, primary graft dysfunction remains a major obstacle because it can cause bronchiolitis obliterans and mortality. Pulmonary vasodilators have been used as an adjunct therapy for heart or lung transplantation, mainly to treat pulmonary hypertension, right ventricular failure, and associated refractory hypoxemia. Among pulmonary vasodilators, inhaled nitric oxide is unique in that it is selective in pulmonary circulation and causes fewer systemic complications such as hypotension, flushing, or coagulopathy. Nitric oxide is expected to prevent or attenuate primary graft dysfunction by decreasing ischemia-reperfusion injury in lung transplantation. However, when considering the long-term benefit of these medications, little evidence supports their use in heart or lung transplantation. Current guidelines endorse inhaled vasodilators for managing immediate postoperative right ventricular failure in lung or heart transplantation, but no guidance is offered regarding agent selection, dosing, or administration. This review presents the current evidence of inhaled nitric oxide in lung or heart transplantation as well as comparisons with other pulmonary vasodilators including cost differences in consideration of economic pressures to contain rising pharmacy costs.