Alpha-Gal Syndrome and Cardiac Surgery.

Galactose-alpha-1,3-galactose (alpha-gal) is a carbohydrate expressed by all mammals except for humans and certain old-world primates. It can be found in a plethora of products derived from mammals, including milk, organs, skeletal muscle and gelatin, in addition to products prepared with mammalian cells or constituents. In the late 2000s, an association between tick bites and the development of immunoglobulin E antibodies to the alpha-gal carbohydrate was discovered. The term "alpha-gal syndrome" (AGS) was then coined to describe allergic reactions to mammalian meat or other alpha-gal-containing products derived from mammals. Symptoms are often delayed several hours from consumption and can be urticarial and/or gastrointestinal. Medications and bioprosthetic inserts derived from mammals were also noted to cause allergic reactions in affected patients. Cardiac surgery, in particular, is considered high risk, given that unfractionated heparin has a bovine or porcine origin and is administered in large doses for cardiopulmonary bypass. Bioprosthetic valves have similar origins and risks. Awareness of AGS in cardiac surgery patients can lead to decreased risk preoperatively and inform management perioperatively and postoperatively. In this narrative review, we have reviewed the published literature relevant to AGS in patients undergoing cardiac surgery and shared our treatment approach.

Medical Malpractice Claims Related to Performance of Transesophageal Echocardiography by Anesthesiologists.

More than 300,000 adults have cardiac surgery in the United States annually, and most undergo intraoperative transesophageal echocardiography (TEE). This patient population is often older with multiple comorbidities, increasing their risk for complications for even routine procedures. Major morbidity or mortality caused by TEE is rare, and it is unknown how often such complications lead to malpractice lawsuits. The authors identified 13 cases out of 2,564 in a closed claims database that involved TEE and reviewed their etiology. Esophageal injury accounted for most of the suits, and only 2 were related to diagnosis. Most expert reviews deemed the care provided by the anesthesiologist to be appropriate.

Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study-protocol for a phase 3, randomized, controlled trial.

BACKGROUND: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. METHODS: ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. DISCUSSION: RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.

Undiagnosed Factor VII Deficiency in Cardiac Surgery Complicated by Bleeding: A Case Report.

Rare bleeding disorders in the perioperative period call for targeted resuscitation strategies. Factor VII deficiency, for instance, is often corrected with exogenous administration of recombinant factor VIIa. This activated clotting factor, initially designed for patients with hemophilia A or B with factor inhibitors, is gaining popularity as a salvage therapy for severe and persistent traumatic and surgical bleeding. This article describes the management of a cardiothoracic surgical patient with undiagnosed isolated factor VII deficiency who experienced significant postoperative bleeding which subsided after the administration of recombinant factor VIIa. In this case, EXTEM failed to detect a clotting factor deficiency.

Impact of body mass index on surgical case durations in an academic medical center.

STUDY OBJECTIVE: To investigate the association between patient body mass index (BMI) and operating room duration. DESIGN: Retrospective cohort analysis. SETTING: Demographic data and anesthesia/surgical times for adult surgical patients at University of Virginia Health between August 2017 and February 2019 were collected and analyzed. PATIENTS: A total of 31,548 cases were included in the final analysis. 55% of patients were female, and 51% were classified as ASA Physical Status 2. The mean operating room (OR) duration was 144.2 min ± 112.7 (median = 118, IQR = 121). Orthopedic surgery (32%) was the most common surgery. MEASUREMENTS: Linear mixed effects models were used to examine whether procedure intervals differed across three BMI categories (BMI < 30, 30 ≤ BMI < 40, BMI ≥ 40), considering within-surgeon correlations. Surgical times were log-transformed to correct for positive skewness. MAIN RESULTS: The average time in the operating room was longer for patients with higher BMI (mean ± SD [median, IQR] = 139.5 ± 111.2 [113.0, IQR = 114], 150.2 ± 115.4 [125, IQR = 127], and 153.1 ± 111.1 [130, IQR = 134] for BMI < 30, 30 ≤ BMI < 40, and BMI ≥ 40), respectively. We found a 2% [95% CI = 1-3%] and 3% [95% CI = 1-5%] increase in OR time for 30 ≤ BMI < 40 and BMI ≥ 40, respectively, compared to BMI < 30, after controlling for within-surgeon correlations and covariates. The excess time was primarily determined by anesthesia times. CONCLUSION: In an academic hospital, patients with BMI ≥ 30 required more time in the operating room than patients with BMI < 30, when controlling for confounders. This information can be incorporated into modern-day OR scheduling software, potentially resulting in more accurate case duration estimates that reduce waiting and improve OR efficiency.

Bedside Clinician's Guide to Pulmonary Artery Catheters.

BACKGROUND: Pulmonary artery catheters provide important information about cardiac function, mixed venous oxygenation, and right-sided pressures and potentially provide temporary pacing ability. OBJECTIVE: To provide bedside clinicians with guidance for techniques to insert right heart monitors and devices, describe risk factors for difficult insertion and contraindications to placement, and provide updates on new technologies that may be encountered in the intensive care unit. METHODS: An extensive literature review was performed. Experienced clinicians were asked to identify topics not addressed in the literature. RESULTS: Advanced imaging techniques such as transesophageal echocardiography or fluoroscopy can supplement traditional pressure waveform-guided insertion when needed, and several other techniques can be used to facilitate passage into the pulmonary artery. Caution is warranted when attempting insertion in patients with right-sided masses or preexisting conduction abnormalities. New technologies include a pacing catheter that anchors to the right ventricle and a remote monitoring device that is implanted in the pulmonary artery. DISCUSSION: Bedside clinicians should be aware of risk factors such as atrial fibrillation with dilated atria, decreased ventricular function, pulmonary hypertension, and right-sided structural abnormalities that can make pulmonary artery catheter insertion challenging. Clinicians should be familiar with advanced techniques and imaging options to facilitate placement. CONCLUSION: The overall risk of serious complications with right heart catheter placement and manipulation is low and often outweighed by its benefits, specifically pressure monitoring and pacing.

Factor VIII: A Dynamic Modulator of Hemostasis and Thrombosis in Trauma.

A trace amount of thrombin cleaves factor VIII (FVIII) into an active form (FVIIIa), which catalyzes FIXa-mediated activation of FX on the activated platelet surface. FVIII rapidly binds to von Willebrand factor (VWF) after secretion and becomes highly concentrated via VWF-platelet interaction at a site of endothelial inflammation or injury. Circulating levels of FVIII and VWF are influenced by age, blood type (nontype O > type O), and metabolic syndromes. In the latter, hypercoagulability is associated with chronic inflammation (known as thrombo-inflammation). In acute stress including trauma, releasable pools of FVIII/VWF are secreted from the Weibel-Palade bodies in the endothelium and then augment local platelet accumulation, thrombin generation, and leukocyte recruitment. Early systemic increases of FVIII/VWF (>200% of normal) levels in trauma result in a lower sensitivity of contact-activated clotting time (activated partial thromboplastin time [aPTT] or viscoelastic coagulation test [VCT]). However, in severely injured patients, multiple serine proteases (FXa plasmin and activated protein C [APC]) are locally activated and may be systemically released. Severity of traumatic injury correlates with prolonged aPTT and elevated activation markers of FXa, plasmin, and APC, culminating in a poor prognosis. In a subset of acute trauma patients, cryoprecipitate that contains fibrinogen, FVIII/VWF, and FXIII is theoretically advantageous over purified fibrinogen concentrate to promote stable clot formation, but comparative efficacy data are lacking. In chronic inflammation or subacute phase of trauma, elevated FVIII/VWF contributes to the pathogenesis of venous thrombosis by enhancing not only thrombin generation but also augmenting inflammatory functions. Future developments in coagulation monitoring specific to trauma patients, and targeted to enhancement or inhibition of FVIII/VWF, are likely to help clinicians gain better control of hemostasis and thromboprophylaxis. The main goal of this narrative is to review the physiological functions and regulations of FVIII and implications of FVIII in coagulation monitoring and thromboembolic complications in major trauma patients.

Abdominal Aortic Aneurysms (Etiology, Epidemiology, and Natural History).

Abdominal aortic aneurysm is a potentially lethal condition that is decreasing in frequency as tobacco use declines. The exact etiology remains unknown, but smoking and other perturbations seem to trigger an inflammatory state in the tunica media. Male sex and advanced age are clear demographic risk factors for the development of abdominal aortic aneurysms. The natural history of this disease varies, but screening remains vital as it is rarely diagnosed on physical examination, and elective repair (most commonly done endovascularly) offers significant morbidity and mortality advantages over emergent intervention for aortic rupture.

Perioperative acetaminophen is associated with reduced acute kidney injury after cardiac surgery.

BACKGROUND: Cardiac surgery-associated acute kidney injury (AKI) is associated with increased postoperative morbidity and mortality. Evidence suggests an association between perioperative acetaminophen administration and decreased incidence of postoperative AKI in pediatric cardiac surgery patients; however, an effect in adults is unknown. METHODS: All patients (n = 6192) undergoing coronary and/or valve surgery with a recorded Society of Thoracic Surgeons (STS) risk score at our institution between 2010 and 2018 were stratified by acetaminophen exposure on the day of surgery using institutional pharmacy records. AKI was determined using the Kidney Disease: Improving Global Outcomes (KDIGO) staging criteria. Logistic regression was used to analyze the association between perioperative acetaminophen and postoperative kidney injury or STS major morbidity. A sensitivity analysis using propensity score matching on the STS predicted risk of renal failure and cardiopulmonary bypass time was performed to account for time bias. RESULTS: Perioperative acetaminophen exposure was associated with lower odds of stage 1 to 3 acute kidney injury (odds ratio [OR], 0.68; 95% CI, 0.56-0.83; P < .001) and decreased prolonged postoperative ventilation (OR, 0.53; 95% CI, 0.37-0.76; P < .001). A sensitivity analysis provided well-balanced (standard mean difference <0.10) groups of 401 pairs, in which acetaminophen was associated with a decreased incidence of postoperative AKI (OR, 0.7; 95% CI, 0.52-0.94; P = .016). CONCLUSIONS: Exposure to acetaminophen on the day of surgery was associated with a decreased incidence of AKI in our patients undergoing cardiac surgery. These data serve as a measure of effect size to further explore the therapeutic potential of acetaminophen to reduce postoperative AKI after cardiac surgery and to elucidate the mechanisms involved.

Red Blood Cell Transfusion and Postoperative Infection in Patients Having Coronary Artery Bypass Grafting Surgery: An Analysis of the Society of Thoracic Surgeons Adult Cardiac Surgery Database.

BACKGROUND: Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure in the world and up to one-third of patients are transfused red blood cells (RBCs). RBC transfusion may increase the risk for health care-associated infection (HAI) after CABG, but previous studies have shown conflicting results and many did not establish exposure temporality. Our objective was to explore whether intraoperative RBC transfusion is associated with increased odds of postoperative HAI. We hypothesized that intraoperative RBC transfusion would be associated with increased odds of postoperative HAI. METHODS: We performed an observational cohort study of isolated CABG patients in the Society of Thoracic Surgeons adult cardiac surgery database from July 1, 2017, to June 30, 2019. The exposure was intraoperative RBC transfusion modeled as 0, 1, 2, 3, or 4+ units. The authors focused on intraoperative RBC transfusion as a risk factor, because it has a definite temporal relationship before postoperative HAI. The study's primary outcome was a composite HAI variable that included sepsis, pneumonia, and surgical site infection (both deep and superficial). Mixed-effects modeling, which controlled for hospital as a clustering variable, was used to explore the relationship between intraoperative RBC transfusion and postoperative HAI. RESULTS: Among 362,954 CABG patients from 1076 hospitals included in our analysis, 59,578 patients (16.4%) received intraoperative RBCs and 116,186 (32.0%) received either intraoperative or postoperative RBCs. Risk-adjusted odds ratios for HAI in patients who received 1, 2, 3, and 4+ intraoperative RBCs were 1.11 (95% confidence interval [CI], 1.03-1.20; P = .005), 1.13 (95% CI, 1.05-1.21; P = .001), 1.15 (95% CI, 1.04-1.27; P = .008), and 1.14 (95% CI, 1.02-1.27; P = .02) compared to patients who received no RBCs. CONCLUSIONS: Intraoperative RBC transfusion is associated with a small increase in odds of HAI in CABG patients. Future studies should explore whether reductions in RBC transfusion can also reduce HAIs.

Heparin Insensitivity and Thrombotic Risk Associated With Sequential Uses of Prothrombin Complex Concentrate and Andexanet Alfa for Apixaban Reversal During Acute Type A Aortic Dissection Repair: A Case Report.

The management of patients on direct oral anticoagulants (DOACs) who require emergent cardiac surgery is slowly evolving. The introduction of andexanet alfa, a novel antidote for apixaban and rivaroxaban, added a specific reversal agent to our armamentarium, but its safety and efficacy are still being investigated. We report 2 patients on DOAC treatment who required emergency cardiac surgery. Both received perioperative andexanet alfa together with prothrombin complex concentrate (PCC) at some time during 6 hours before operative management. Heparin resistance was noted in each instance, and pump thrombosis developed in 1 case.

Red Blood Cell Transfusion and Postoperative Delirium in Hip Fracture Surgery Patients: A Retrospective Observational Cohort Study.

BACKGROUND: Patients having hip fracture surgery are at high risk for postoperative delirium. Red blood cell (RBC) transfusion may increase postoperative delirium risk by causing neuroinflammation. We hypothesized that RBC transfusion would be associated with postoperative delirium in patients having hip fracture surgery. METHODS: An observational cohort study was performed using the United States National Surgical Quality Improvement Program (NSQIP) participant use files for hip fracture from 2016 to 2018. Propensity score analysis and inverse probability of treatment weighting (IPTW) were used to reduce bias from confounding. An IPTW adjusted odds ratio for developing postoperative delirium was calculated for patients who received RBC transfusion during surgery or in the 72 hours after. RESULTS: There were 20,838 patients who had eligible current procedural terminology (CPT) codes for primary hip fracture surgery and complete study data. After employing strict exclusions to balance covariates and reduce bias, 3,715 patients remained in the IPTW cohort. Of these, 626 patients (16.9%) received RBC transfusion and 665 patients (17.9%) developed postoperative delirium. IPTW adjustment led to good covariate balance between patients who received RBC transfusion and those who did not. Patients who received RBC transfusion had significantly higher odds of postoperative delirium, IPTW adjusted odds ratio = 1.21, 95% CI = 1.03 to 1.43, and P = 0.02. Discharge location also differed significantly between patients who received RBC transfusion and those who did not (P < 0.001) with in-hospital mortality or referral to hospice occurring in 1.6% of patients who received RBC transfusion and 1.3% of patients who were not transfused. CONCLUSION: RBC transfusion is associated with increased odds of postoperative delirium after hip fracture surgery and may be associated with worse clinical outcome.

Impact of Preoperative Platelet Count on Bleeding Risk and Allogeneic Transfusion in Multilevel Spine Surgery.

STUDY DESIGN: This was an observational cohort study of patients receiving multilevel thoracic and lumbar spine surgery. OBJECTIVE: The aim of this study was to identify which patients are at high risk for allogeneic transfusion which may allow for better preoperative planning and employment of specific blood management strategies. SUMMARY OF BACKGROUND DATA: Multilevel posterior spine surgery is associated with a significant risk for major blood loss, and allogeneic blood transfusion is common in spine surgery. METHODS: A univariate logistic regression model was used to identify variables that were significantly associated with intraoperative allogeneic transfusion. A multivariate forward stepwise logistic regression model was then used to measure the adjusted association of these variables with intraoperative transfusion. RESULTS: Multilevel thoracic and lumbar spine surgery was performed in 921 patients. When stratifying patients by preoperative platelet count, patients with pre-operative thrombocytopenia and severe thrombocytopenia had a significantly higher rate of transfusion than those who were not thrombocytopenic. Furthermore, those with severe thrombocytopenia had a higher rate of red blood cells, fresh frozen plasma, and platelet transfusion than those with higher platelet counts. Multivariate logistic regression found that preoperative platelet count was the most significant contributor to transfusion, with a platelet count ≤100 having an adjusted odds ratio (OR) of transfusion of 4.88 (95% confidence interval [CI] 1.58-15.02, P = 0.006). Similarly, a platelet count between 101and 150 also doubled the risk of transfusion with an adjusted OR of 2.02 (95% CI 1.01-4.04, P = 0.047). The American Society of Anesthesiologists classification score increased the OR of transfusion by 2.5 times (OR = 2.52, 95% CI 1.54-4.13), whereas preoperative prothrombin time and age minimally increased the risk. CONCLUSION: Preoperative thrombocytopenia significantly contributes to intraoperative transfusion in multilevel thoracic lumbar spine surgery. Identifying factors that may increase the risk for transfusion could be of great benefit in better preoperative counseling of patients and in reducing overall cost and postoperative complications by implementing strategies and techniques to reduce blood loss and blood transfusions. LEVEL OF EVIDENCE: 2.

Peripheral Cardiopulmonary Bypass in Two Patients With Symptomatic Tracheal Masses: Perioperative Challenges.

Tracheal tumors or masses causing critical airway obstruction require resection for symptom relief. However, the location and extent of these tumors or masses often preclude conventional general anesthesia and tracheal intubation. Peripheral cardiopulmonary bypass often is required before anesthetizing these patients. Herein, two cases of patients with tracheal masses, in whom awake peripheral cardiopulmonary bypass was instituted, are reported. The first case was that of an obese male child weighing 102 kg, with tracheal rhinoscleroma, who developed Harlequin, or north-south, syndrome after institution of femorofemoral venoarterial partial cardiopulmonary bypass. The second case was that of a female patient with adenoid cystic carcinoma of the trachea causing near-total central airway occlusion. She had severe pulmonary artery hypertension, which prevented the use of venovenous bypass. Instead, femoral vein-axillary artery venoarterial bypass was established to avoid Harlequin syndrome. Some of the challenges encountered were the development of Harlequin syndrome with risk of myocardial and cerebral ischemia, type and conduct of extracorporeal bypass, choice of monitoring sites, and provision of regional anesthesia for peripheral extracorporeal cannulations. Management of such patients needs frequent troubleshooting and multidisciplinary coordination for a successful surgical outcome.