Association Between Preoperative Anemia and Cognitive Function in a Large Cohort Study of Older Patients Undergoing Elective Surgery.

BACKGROUND: The etiology of anemia has tremendous overlap with the disease states responsible for cognitive decline. We used data from a perioperative database of older adults undergoing elective surgery with anesthesia to (1) examine relationships among preoperative anemia blood markers, preoperative screeners of cognitive function, and chronic disease status; and (2) examine the relationship of these factors with operative outcomes. The primary goal of this study was to investigate the association between preoperative anemia blood markers and cognition measured by a preoperative cognitive screener. Secondary goals were to (1) examine the relationship between preoperative anemia blood markers and chronic disease states (ie, American Society of Anesthesiologists [ASA] and frailty), and (2) investigate the relationship of preoperative anemia blood markers and cognition with operative outcomes (ie, discharge disposition, 1-year mortality, number of surgical complications, length of hospital stay, and length of intensive care unit [ICU] stay). METHODS: Data were collected at the University of Florida Health Shands Presurgical Center and the Perioperative Cognitive Anesthesia Network clinic within the electronic medical record. Patients 65 years of age or older were included if they had a preoperative hemoglobin (Hgb) value and a preoperative screening. Nonparametric methods were used for bivariate analysis. Logistic regression was used for the simultaneous examination of variables associated with nonhome discharge and 1-year mortality. Primary outcomes were discharge disposition and 1-year mortality. Secondary outcomes were number of surgical complications and length of hospital and ICU stay. RESULTS: Of 14,795 patients cognitively assessed, 8643 met the inclusion criteria. Of these, 26.7% were anemic, with 16.8%, 9.5%, and 0.4% having mild, moderate, and severe anemia, respectively. The Spearman correlation coefficient [95% confidence interval, CI] between the Hgb level and the clock drawing time (CDT) was -.15 [-.17 to -.13] (P < .0001) indicating that a lower Hgb level was associated with cognitive vulnerability. Hgb was also negatively correlated with the ASA physical status classification, patient Fried Frailty Index, and hospital and ICU length of stay. In the multivariable model, age, surgical service, ASA and Fried Frailty Index significantly predicted nonhome discharge. Furthermore, age, surgical service, ASA, Fried Frailty Index, and Hgb independently predicted death within 1 year of surgery. The odds of death, adjusted for ASA, Fried Frailty, and covariates, were 2.7 times higher for those in the mild anemic group compared to those who were not anemic (odds ratio [OR], 2.7, 95% CI, [2.1-3.5]). The odds of death, adjusted for ASA, Fried Frailty, and covariates, were 3.6 times higher for those in the moderate/severe anemic group compared to those who were not anemic (OR, 3.6, 95% CI, [2.7-4.9]). CONCLUSIONS: In this first medicine study, we established relationships among anemia, preoperative markers of frailty and cognition, and chronic disease states in a large cohort of older patients undergoing elective surgery in a large tertiary medical center. We found that anemia, cognitive vulnerability, and chronic health disease states predicted death within 1 year of surgery, and that these preoperative factors negatively contribute to surgical outcomes such as time in the ICU, length of hospital stay, nonhome discharge, and 1-year mortality. The World Health Organization (WHO) and many academic medical societies have urged the adoption of patient blood management (PBM) disciplines, yet anemia is not routinely optimized as a preoperative risk factor. Given the well-defined association between preoperative anemia and postoperative morbidity and mortality, performing elective surgery on an untreated anemic patient should be considered substandard care. With established safe and effective treatment regimens, iron deficiency anemia is a modifiable preoperative risk factor that should be addressed before elective surgery.

Differences between patients in whom physicians agree versus disagree about the preoperative diagnosis of heart failure.

STUDY OBJECTIVE: To quantify preoperative heart failure (HF) diagnostic agreement and identify characteristics of patients in whom physicians agreed versus disagreed about the diagnosis. DESIGN: Observational cohort study. SETTING: Patients undergoing major non-cardiac surgery at an academic center between 2015 and 2019. PATIENTS: 40,659 patients undergoing major non-cardiac surgery, among which a stratified subsample of 1018 patients with and without documented HF was reviewed. INTERVENTIONS: Via a panel of physicians frequently managing patients with HF (cardiologists, cardiac anesthesiologists, intensivists), detailed chart reviews were performed (two per patient; median review time 32 min per reviewer per patient) to render adjudicated HF diagnoses. MEASUREMENTS: Adjudicated diagnostic agreement measures (percent agreement, Krippendorf's alpha) and univariate comparisons (standardized differences) between patients in whom physicians agreed versus disagreed about the preoperative HF diagnosis. MAIN RESULTS: Among patients with documented HF, physicians agreed about the diagnosis in 80.0% of cases (consensus positive), disagreed in 13.8% (disagreement), and refuted the diagnosis in 6.3% (consensus negative). Conversely, among patients without documented HF, physicians agreed about the diagnosis in 88.0% (consensus negative), disagreed in 8.4% (disagreement), and refuted the diagnosis in 3.6% (consensus positive). The estimated agreement for the 40,659 cases was 91.1% (95% CI 88.3%-93.9%); Krippendorff's alpha was 0.77 (0.75-0.80). Compared to patients in whom physicians agreed about a HF diagnosis, patients in whom physicians disagreed exhibited fewer guideline-defined HF diagnostic criteria. CONCLUSIONS: Physicians usually agree about HF diagnoses adjudicated via chart review, although disagreement is not uncommon and may be partly explained by heterogeneous clinical presentations. Our findings inform preoperative screening processes by identifying patients whose characteristics contribute to physician disagreement via chart review. Clinical Trial Number / Registry URL: Not applicable.

Successful living donor liver transplantation in a patient with hemophilia A and factor VIII inhibitor: A case report with perioperative recommendations.

Liver transplantation in patients with end-stage liver disease and coexisting hemophilia A has been described. Controversy exists over perioperative management of patients with factor VIII inhibitor predisposing patients to hemorrhage. We describe the case of a 58-year-old man with a history of hemophilia A and factor VIII inhibitor, eradicated with rituximab prior to living donor liver transplantation without recurrence of inhibitor. We also provide perioperative management recommendations from our successful multidisciplinary approach.

Global sources of cryoprecipitate demonstrate variability in coagulant factor levels and functional hemostasis.

Cryoprecipitate (cryo) is a plasma-derived blood product utilized during trauma resuscitation, surgery, and other major bleeding. Although local quality control metrics exist, inherent donor variability, and processing may confer differences in hemostatic effect between sources. The purposes of this study were to quantify procoagulant content in three global sources of cryo and evaluate their functional hemostatic effect. In this Institutional Review Board exempt study, 24 units of group A cryo from three different sources, American Red Cross single donor and pooled donor, Australian Red Cross single donor, Southwestern United States single donor, and Southwest pooled donor, were evaluated. Procoagulant factors were quantified from each source using ELISA and automated clot-based assays. Functional hemostasis was evaluated using rotational Thromboelastometry (ROTEM). Microparticles isolated from cryo units were enumerated and evaluated for cellular origin by flow cytometry, as well as their capacity to support thrombin generation. Southwestern United States single donor units demonstrated highest levels of fibrinogen, fibronectin, factor VIII, and von Willebrand factor in the selected units. In the coagulopathy model, successive doses from all cryo units were significantly correlated to decreasing coagulation time (P = 0.0100), and increasing maximum clot firmness (P = 0.0002) and alpha angle (P = 0.0009). Southwest pooled donor demonstrated significantly shorter coagulation time at all three doses (P = 0.02) than other sources. Microparticles support prothrombinase activity and thrombin generation. In this study of global cryo sources, procoagulant activity and in-vitro clot formation varied by source. This could be explained by variance in production and storage protocols. Further study is warranted to assess functional variance in cryo to optimize and standardize the use of cryo products.

Modulation of red blood cell oxygen affinity with a novel allosteric modifier of hemoglobin is additive to the Bohr effect.

PURPOSE: The Bohr effect describes hemoglobin's affinity for oxygen dependent on solution pH. Within pH range 6.0-8.5, hemoglobin's oxygen affinity decreases with decreasing pH. This results in increased oxygen delivery to metabolically active, acidic tissues and improved oxygen uptake in basic regions including lung tissue. Myo-Inositol tripyrophosphate (ITPP) translocates the erythrocyte membrane and allosterically modifies hemoglobin (Hb). We tested the hypothesis that ITPP does not abrogate the Bohr effect. METHODS: Experiments were conducted to determine the effect of increasing concentrations of ITPP on P50 with varying pH. We incubated 10 mL red blood cells at 37 °C for 1 h with ITPP concentrations from 0 to 240 mM. The Clark oxygen electrode (Hemox-Analyzer; TCS Scientific, New Hope, PA) determined oxygen affinity of each sample, in triplicate, using buffers pH 6.8, 7.4, and 7.6. A mixed linear regression model with fixed effects for ITPP concentration and pH was used. RESULTS: Increasing ITPP concentration and decreasing pH increased P50 (p < 0.0001 for ITPP concentration, p < 0.0001 for pH). ITPP modulated increased P50 in normal pH (7.4) and acidic condition pH (6.8); with no effect at alkaline pH (7.6). CONCLUSION: The Bohr effect is conserved, with ITPP augmenting the decreased oxygen affinity seen with tissue acidosis, while not affecting oxygen affinity in conditions similar to a pulmonary microenvironment.

The effect of pathogen inactivation on cryoprecipitate: a functional and quantitative evaluation.

BACKGROUND: As a pooled donor blood product, cryoprecipitate (cryo) carries risks of pathogen transmission. Pathogen inactivation (PI) improves the safety of cryoprecipitate, but its effects on haemostatic properties remain unclear. This study investigated protein expression in samples of pathogen inactivated cryoprecipitate (PI-cryo) using non-targeted quantitative proteomics and in vitro haemostatic capacity of PI-cryo. MATERIALS AND METHODS: Whole blood (WB)- and apheresis (APH)-derived plasma was subject to PI with INTERCEPT® Blood System (Cerus Corporation, Concord, CA, USA) and cryo was prepared from treated plasma. Protein levels in PI-cryo and paired controls were quantified using liquid chromatography-tandem mass spectrometry. Functional haemostatic properties of PI-cryo were assessed using a microparticle (MP) prothrombinase assay, thrombin generation assay, and an in vitro coagulopathy model subjected to thromboelastometry. RESULTS: Over 300 proteins were quantified across paired PI-cryo and controls. PI did not alter the expression of coagulation factors, but levels of platelet-derived proteins and platelet-derived MPs were markedly lower in the WB PI-cryo group. Compared to controls, WB (but not APH) cryo samples demonstrated significantly lower MP prothrombinase activity, prolonged clotting time, and lower clot firmness on thromboelastometry after PI. However, PI did not affect overall thrombin generation variables in either group. DISCUSSION: Data from this study suggest that PI via INTERCEPT® Blood System does not significantly impact the coagulation factor content or function of cryo but reduces the higher MP content in WB-derived cryo. PI-cryo products may confer benefits in reducing pathogen transmission without affecting haemostatic function, but further in vivo assessment is warranted.

Rejuvenation solution as an adjunct cold storage solution maintains physiological haemoglobin oxygen affinity during early-storage period of red blood cells.

BACKGROUND: Red blood cell (RBC) units accumulate morphologic and metabolic lesions during storage before transfusion. Pyruvate-inosine-phosphate-adenine (PIPA) solutions (Rejuvesol, Biomet, Warsaw, IN) can be incubated with RBC units to mitigate storage lesions. This study proposes a PIPA treatment process, termed cold 'rejuvenation', using Rejuvesol as an adjunct additive solution, to prevent biomechanical storage lesions while avoiding the 1 h PIPA incubation required with standard PIPA treatment. We compared the efficacy of cold to standard 'rejuvenation' in improving metabolic lesions that occur during cold storage of RBCs, without altering function. METHODS: Twelve leucoreduced, A-positive RBC units were obtained. Each unit was aliquoted into either control (standard storage), washed (W), standard rejuvenation (SR) or cold rejuvenation (CR) groups, the latter two requiring washing. A volume-adjusted dose of Rejuvesol was instilled into the CR group upon receipt (Day 3). After 15 days of storage, p50, RBC deformability, in-bag haemolysis and mechanical fragility were analysed. 'Any treatment' is defined as W, SR and CR, with comparisons in reference to control. RESULTS: Higher p50s were seen in rejuvenated groups (>30 mmHg vs. <19 mmHg; P < 0·0001). Any treatment significantly increased elongation index (P = 0·034) but did not significantly increase in-bag haemolysis (P = 0·062). Mechanical fragility was not significantly different between groups (P = 0·055) at baseline, but the control (CTL) group was more fragile after 2 h in a cardiac bypass simulation than any treatment (P < 0·0001). CONCLUSIONS: This study demonstrates that rejuvenation (standard or cold) prevents the leftward p50 shift of storage lesions without detrimental effect on RBC deformity, in-bag haemolysis or mechanical fragility.

Evaluation of a Standardized Cardiac Athletic Screening for National Collegiate Athletic Association (NCAA) Athletes.

INTRODUCTION: Sudden cardiac death is a rare cause of death in young athletes. Current screening techniques include history and physical exam (H and P), with or without an electrocardiogram (ECG). Adding point of care cardiac ultrasound has demonstrated benefits, but there is limited data about implementing this technology. We evaluated the feasibility of adding ultrasound to preparticipation screening for collegiate athletes. METHODS: We prospectively enrolled 42 collegiate athletes randomly selected from several sports. All athletes were screened using a 14-point H and P based on 2014 American College of Cardiology (ACC) and American Heart Association (AHA) guidelines, ECG, and cardiac ultrasound. RESULTS: We screened 11 female and 31 male athletes. On ultrasound, male athletes demonstrated significantly larger interventricular septal wall thickness (p = 0.002), posterior wall thickness (p <0.001) and aortic root breadth (p = 0.002) compared to females. Based on H and P and ECGs alone and a combination of H and P with ECG, no athletes demonstrated a positive screening for cardiac abnormalities. However, with combined H and P, ECG, and cardiac ultrasound, one athlete demonstrated positive findings. CONCLUSIONS: We believe that adding point of care ultrasound to the preparticipation exam of college athletes is feasible. This workflow may provide a model for athletic departments' screening.

Interval decline in hemoglobin A is associated with annual clinical event rate in sickle cell anemia patients receiving maintenance apheresis RBC exchange.

BACKGROUND: Apheresis red blood cell (RBC) exchange (RCE) is a standard intervention for patients with sickle cell anemia (SCA) who have had previous thromboembolic stroke or intractable chronic pain. Replacing sickling cells with those containing hemoglobin A (HbA) minimizes microvascular pathophysiology that produces clinical crises. Limited data exist regarding the interval changes in HbA between transfusions. We sought to describe the HbA decrement between RCE procedures and its relationship to clinical status. STUDY DESIGN AND METHODS: SCA patients (all hemoglobin SS disease) treated with maintenance RCE (n = 21) over a 15-month period at two neighboring institutions were retrospectively reviewed. Time-normalized daily HbA decrement was calculated to reflect loss of transfused RBCs, and annual events of either emergency department or hospital admissions for SCA complications were noted. Associations between HbA decrement and laboratory measures were calculated using mixed linear regression models and unpaired t test was used to compare HbA decrement between high and low event rate groups. RESULTS: A total of 31 events were recorded, and mean HbA decrement per day was 0.77 ± 0.16%. The mean interval between RCEs was 36 ± 12 days. Patients with more annual events exhibited a significantly greater daily HbA decrement (p = 0.007). No significant association between RBC unit age and HbA decrement or annual event rate was observed. CONCLUSIONS: Patients exhibiting greater daily HbA decrement were more likely to have multiple emergency department visits or admissions for sickling crises. Modulating HbA decrement may merit study as an intermediate metric for interventions to improve outcomes in hemoglobin SS disease.

Massive transfusion in the pediatric population: A systematic review and summary of best-evidence practice strategies.

BACKGROUND: Pediatric patients require massive transfusion (MT) in a variety of settings. Multiple studies of adult MT support balanced ratio transfusion to improve outcomes; however, it is unclear if these findings can be extrapolated to pediatric populations. The use of balanced transfusion ratios, MT protocols, hemostatic adjuncts, and even the definition of a MT in children are all open questions. This review presents details of care from current practices in pediatric MT and summarizes practice strategies while providing insight from our single-center experience. METHODS: PubMed, EMBASE, and Web of Science were searched using MeSH index and free-text terms for articles from 1946 to 2017. Articles were independently reviewed by two reviewers. Studies were assessed for definition of MT, factors predicting MT, MT complications, blood product ratios, hemostatic adjuncts, protocol logistics, and clinical outcomes. RESULTS: A heterogeneous composite of 29 articles was included in the analysis. Of these, 45% reported a formal transfusion protocol or adopted one during the study. Seven unique definitions of pediatric MT were reported; the most common was >1 total blood volume within 24 hours. A total of 18,369 patients were assessed, and 1,163 received MT (6.3%). Overall mortality for patients requiring MT in studies reporting mortality was high (range 14.7% to 51.2%). We identified 14 patients receiving MT at our center with an age range of 8 months to 18 years and average transfusion of 38.1 mL/kg red blood cells (range: 22.1 mL/kg to 156.7 mL/kg). CONCLUSIONS: Current practices of pediatric MT demonstrate a variety of site-specific interventions with a persistently high mortality rate. A national focus on improving techniques of MT in children has the potential to save the lives of these children. LEVEL OF EVIDENCE: Systematic review, levels IV and V.

Health Career Academy: Addition of a Surgical Case-Based Learning Curriculum Captures the Interest of High School Students.

OBJECTIVE: The Health Career Academy (HCA) is a national program which provides a structure to introduce underserved high school students to healthcare careers. Utilizing the HCA framework, we adapted the curriculum to emphasize surgical cases and invited physicians to enrich the learning experience. DESIGN, SETTING, AND PARTICIPANTS: Medical students adapted a surgical case-based learning (CBL) curriculum at a local high school serving students from a primarily ethnic minority and low-income community (61% Black, 20% Hispanic; 58% free or reduced lunch). Each grade level received a minimum of ten, 90-minute CBL sessions. Expert faculty lecturers supplemented lessons. Medical student volunteers and 10th and 11th grade students completed postsemester surveys. RESULTS: Over four semesters, HCA held 44 sessions, with 81 students graduating from the program. A total of 66% of sessions featured at least one faculty volunteer. A total of 36 students in 10th and 11th grade and 15 medical student volunteers completed postparticipation surveys. A total of 46.2% of 11th grade students previously participated in the 10th grade curriculum. On a scale of 1 to 4, students rated HCA highly in its overview of career options (mean 3.61, [SD 0.5]) and instilling understanding of patient care (3.78 [0.42]). Students enjoyed learning about career paths (3.61 [0.50]) and health topics (3.83 [0.39]). Of 10th and 11th grade students, 100% considered a healthcare career, with 34.8% of 10th and 61.5% of 11th grade students expressing interest in pursuing a surgical specialty. After volunteering, medical students felt like better educators (4.47 [0.64]) and were more likely to pursue teaching roles (4.2 [0.86]). CONCLUSIONS: The Duke HCA chapter implemented the HCA program featuring CBL sessions emphasizing surgical cases. This program engaged minority students and potentially contributed to student interest in surgical careers. It helped to prepare medical students for future teaching roles. An interactive, surgery-focused program may increase the number of minority youth interested in pursuing health careers.

Routine postprocedure ultrasound increases rate of detection of femoral arterial thrombosis in infants after cardiac catheterization.

OBJECTIVES: To examine the effect of implementing postcatheterization ultrasound (US) on femoral arterial thrombosis detection rates and factors associated with thrombosis in infants. BACKGROUND: Although femoral arterial thrombosis is an uncommon complication of cardiac catheterization, it can cause limb threatening complications. Previous studies assessing the utility of postprocedure US to detect thrombosis in infants have utilized US as an adjunct to standard clinical detection methods, are small scale, or include small cohorts of infants within older populations. METHODS: We reviewed institutional records of patients 0-12 months undergoing catheterization from 2007 to 2016. Demographics and procedural data were compared between the thrombosis and non-thrombosis group. Pre- and post-US groups were compared for detected thrombosis rate. Using univariate and multivariable analyses, we identified factors associated with thrombosis. RESULTS: In total, 270 patients underwent 509 catheterizations, with 40 (7.9%) documented thromboses. The rate of thrombus detection in patients younger than 6 months increased from 8.3% to 23.4% (P = 0.006) after implementing routine US. On multivariable analysis, lower weight (P < 0.001), larger arterial sheath size (P < 0.001), and longer procedure duration (P = 0.003) were independently associated with higher odds of thrombosis. CONCLUSIONS: Higher rates of femoral arterial thrombosis detection were observed since implementing an US screening program. Further studies are needed to evaluate age-related changes in hemostasis in this population and how advanced screening methods and anticoagulation protocols may help improve short-term and long-term sequelae of femoral arterial thrombosis.