Sex and race differences of cerebrospinal fluid metabolites in healthy individuals.

INTRODUCTION: Analyses of cerebrospinal fluid (CSF) metabolites in large, healthy samples have been limited and potential demographic moderators of brain metabolism are largely unknown. OBJECTIVE: Our objective in this study was to examine sex and race differences in 33 CSF metabolites within a sample of 129 healthy individuals (37 African American women, 29 white women, 38 African American men, and 25 white men). METHODS: CSF metabolites were measured with a targeted electrochemistry-based metabolomics platform. Sex and race differences were quantified with both univariate and multivariate analyses. Type I error was controlled for by using a Bonferroni adjustment (0.05/33 = .0015). RESULTS: Multivariate Canonical Variate Analysis (CVA) of the 33 metabolites showed correct classification of sex at an average rate of 80.6% and correct classification of race at an average rate of 88.4%. Univariate analyses revealed that men had significantly higher concentrations of cysteine (p < 0.0001), uric acid (p < 0.0001), and N-acetylserotonin (p = 0.049), while women had significantly higher concentrations of 5-hydroxyindoleacetic acid (5-HIAA) (p = 0.001). African American participants had significantly higher concentrations of 3-hydroxykynurenine (p = 0.018), while white participants had significantly higher concentrations of kynurenine (p < 0.0001), indoleacetic acid (p < 0.0001), xanthine (p = 0.001), alpha-tocopherol (p = 0.007), cysteine (p = 0.029), melatonin (p = 0.036), and 7-methylxanthine (p = 0.037). After the Bonferroni adjustment, the effects for cysteine, uric acid, and 5-HIAA were still significant from the analysis of sex differences and kynurenine and indoleacetic acid were still significant from the analysis of race differences. CONCLUSION: Several of the metabolites assayed in this study have been associated with mental health disorders and neurological diseases. Our data provide some novel information regarding normal variations by sex and race in CSF metabolite levels within the tryptophan, tyrosine and purine pathways, which may help to enhance our understanding of mechanisms underlying sex and race differences and potentially prove useful in the future treatment of disease.

Temporal Trends in Difficult and Failed Tracheal Intubation in a Regional Community Anesthetic Practice.

BACKGROUND: When tracheal intubation is difficult or unachievable before surgery or during an emergent resuscitation, this is a critical safety event. Consensus algorithms and airway devices have been introduced in hopes of reducing such occurrences. However, evidence of improved safety in clinical practice related to their introduction is lacking. Therefore, we selected a large perioperative database spanning 2002 to 2015 to look for changes in annual rates of difficult and failed tracheal intubation. METHODS: Difficult (more than three attempts) and failed (unsuccessful, requiring awakening or surgical tracheostomy) intubation rates in patients 18 yr and older were compared between the early and late periods (pre- vs. post-January 2009) and by annual rate join-point analysis. Primary findings from a large, urban hospital were compared with combined observations from 15 smaller facilities. RESULTS: Analysis of 421,581 procedures identified fourfold reductions in both event rates between the early and late periods (difficult: 6.6 of 1,000 vs. 1.6 of 1,000, P < 0.0001; failed: 0.2 of 1,000 vs. 0.06 of 1,000, P < 0.0001), with join-point analysis identifying two significant change points (2006, P = 0.02; 2010, P = 0.03) including a pre-2006 stable period, a steep drop between 2006 and 2010, and gradual decline after 2010. Data from 15 affiliated practices (442,428 procedures) demonstrated similar reductions. CONCLUSIONS: In this retrospective assessment spanning 14 yr (2002 to 2015), difficult and failed intubation rates by skilled providers declined significantly at both an urban hospital and a network of smaller affiliated practices. Further investigations are required to validate these findings in other data sets and more clearly identify factors associated with their occurrence as clues to future airway management advancements. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B635.

CHAMBER: A Regional Performance Improvement CME Initiative for Breast Cancer Health Care Providers.

CHAMBER was a regional educational initiative for providers of care to patients with HER2+ breast cancer. The study goals were to (1) enhance testing for HER2/neu overexpression in patients with invasive breast cancer; (2) increase the appropriate use of targeted therapy for patients with HER2+ breast cancer; and (3) enhance patients' coping ability. This Performance Improvement Continuing Medical Education (PI-CME) initiative included clinical practice assessment, educational activities, and reassessment. Chart review revealed a high rate of HER2 testing (98%) before and after education. Targeted therapy for patients with HER2+ breast cancer declined after the program (from 96% to 61%), perhaps attributable to an increase in awareness of medical reasons to avoid use of targeted therapy. Assessment for patients' emotional coping ability increased after education (from 55% to 76%; P=.01). Rates of testing for HER2 amplification and assessment of emotional well-being after education were consistent with ASCO Quality Oncology Practice Initiative benchmark values. Documentation of actions to address emotional problems remained an area for improvement.

Associations between central nervous system serotonin, fasting glucose, and hostility in African American females.

BACKGROUND: Previous research has shown an association between hostility and fasting glucose in African American women. Central nervous system serotonin activity is implicated both in metabolic processes and in hostility related traits. PURPOSE: The purpose of this study is to determine whether central nervous system serotonin influences the association between hostility and fasting glucose in African American women. METHODS: The study consisted of 119 healthy volunteers (36 African American women, 27 White women, 21 White males, and 35 African American males, mean age 34 ± 8.5 years). Serotonin related compounds were measured in cerebrospinal fluid. Hostility was measured by the Cook-Medley Hostility Scale. RESULTS: Hostility was associated with fasting glucose and central nervous system serotonin related compounds in African American women only. Controlling for the serotonin related compounds significantly reduced the association of hostility to glucose. CONCLUSIONS: The positive correlation between hostility and fasting glucose in African American women can partly be explained by central nervous system serotonin function.

A pilot study on the effect of nasal continuous positive airway pressure on arterial partial pressure of carbon dioxide during spinal anesthesia with intravenous sedation for total knee arthroplasty.

BACKGROUND: Deep sedation of surgical patients may be associated with hypoventilation, airway collapse, and hypercarbia, although the extent of hypercarbia is rarely quantified. In this prospective, randomized, controlled clinical pilot study, we assessed the efficacy of nasal continuous positive airway pressure (nCPAP) for reducing arterial partial pressure of carbon dioxide (PaCO2) among deeply sedated, spontaneously ventilated patients undergoing total knee arthroplasty (TKA) under subarachnoid block (SAB), versus standard airway management in a control group. METHODS: Forty ASA status I-III patients underwent deep sedation with propofol to level 2 on the Modified Observers Assessment of Alertness/Sedation Scale during TKA performed under SAB. Nasal or oral airways were placed at the discretion of the anesthesia team, but they were not used in conjunction with nCPAP. Baseline arterial blood gas analysis (ABG-1) was performed after Modified Observers Assessment of Alertness/Sedation Scale level 2 was reached. Patients were then randomized to receive nCPAP (nCPAP group, N = 20) or standard oxygen mask management (control group, N = 20). A second ABG (ABG-2) was performed 30 minutes later to assess the effect of nCPAP on PaCO2. The primary efficacy end point was change in PaCO2 from baseline to the 30-minute time point. RESULTS: Baseline (ABG-1) PaCO2 values were similar between nCPAP and control groups with median values of 54.5 and 56.1 mm Hg, respectively. There was a significant decline in PaCO2 in the nCPAP group (median of -4.6 mm Hg [10th-90th quantile, -14.55 to 3.85]) as compared with the control group (median of 0.95 mm Hg [-4.75 to 9.85]; P = 0.015; 95% confidence interval [CI] for location shift = -9.5 to -1.3). Within the control group, PaCO2 was similar from ABG-1 to ABG-2 (median [10th-90th quantile] = 56.1 mm Hg [47.2-67.0] vs 56.6 mm Hg [46-68.8]; P = 0.52; 95% CI for the median = -3.4 to 3.4). Forty percent of all patients received an airway before ABG-1. The baseline PaCO2 value of patients receiving an airway was not different from that of patients without an airway (median [10th-90th quantile] = 56.0 mm Hg [46.0-68.4] vs 54.1 mm Hg [45.6-65.6], respectively; P = 0.33; 95% CI for location shift = -2.30 to 7.20). CONCLUSIONS: Deep sedation of TKA patients during SAB resulted in moderate hypercarbia (mean and median PaCO2 = 55). There was a trend showing that nCPAP treatment reduced PaCO2 versus treatment for control group patients receiving standard airway management; however, estimated treatment difference varied widely, from 1.4 to 12.6 mm Hg. Among control group patients, the initial PaCO2 during deep sedation was similar to the PaCO2 when measured after a 30-minute period of continued deep sedation. Finally, baseline PaCO2 among deeply sedated patients who received an airway was not different from that of patients who did not receive an airway.

Update on management strategies for separation from cardiopulmonary bypass.

PURPOSE OF REVIEW: To update the reader about clinical management strategies for separation from cardiopulmonary bypass. A number of new drugs are being introduced in clinical practice, with significant utility in operative patient management. Further, there is increased routine use of complex devices to achieve separation from or avoidance of cardiopulmonary bypass. RECENT FINDINGS: Selected medical and device strategies from the most recent literature will be discussed. First, the rationale for selected innovative agents to achieve myocardial performance is reviewed in four perioperative settings: agents for the management of myocardial dysfunction, vasomotor dysfunction, pulmonary hypertension, and right ventricular failure. Second is an evaluation of less commonly considered aspects of mechanical device use in the context of failure to wean from cardiopulmonary bypass or use to avoid cardiopulmonary bypass. Three devices will be discussed: intra-aortic balloon pump, ventricular assist devices, and extracorporeal membrane oxygenation. SUMMARY: As our pharmacological and technological armamentarium improve, our population ages and procedures are attempted on patients with increasing co-morbid conditions, it will be important to both utilize newer pharmacological agents and consider innovative uses for device implementation to achieve optimal perioperative outcomes.

Central nervous system serotonin and clustering of hostility, psychosocial, metabolic, and cardiovascular endophenotypes in men.

OBJECTIVE: To use measures of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5HIAA) and genotype of a functional polymorphism of the monoamine oxidase A gene promoter (MAOA-uVNTR) to study the role of central nervous system (CNS) serotonin in clustering of hostility, other psychosocial, metabolic and cardiovascular endophenotypes. METHODS: In 86 healthy male volunteers, we evaluated CSF levels of the primary serotonin metabolite 5HIAA and MAOA-uVNTR genotype for association with a panel of 29 variables assessing hostility, other psychosocial, metabolic, and cardiovascular endophenotypes. RESULTS: The correlations of 5HIAA with these endophenotypes in men with more active MAOA-uVNTR alleles were significantly different from those of men with less active alleles for 15 of the 29 endophenotypes. MAOA-uVNTR genotype and CSF 5HIAA interacted to explain 20% and 22% of the variance, respectively, in scores on one factor wherein high scores reflected a less healthy psychosocial profile and a second factor wherein high score reflected increased insulin resistance, body mass index, blood pressure and hostility. In men with less active alleles, higher 5HIAA was associated with more favorable profiles of hostility, other psychosocial, metabolic and cardiovascular endophenotypes; in men with more active alleles, higher 5HIAA was associated with less favorable profiles. CONCLUSIONS: These findings indicate that, in men, indices of CNS serotonin function influence the expression and clustering of hostility, other psychosocial, metabolic and cardiovascular endophenotypes that have been shown to increase risk of developing cardiovascular disease. The findings are consistent with the hypothesis that increased CNS serotonin is associated with a more favorable psychosocial/metabolic/cardiovascular profile, whereas decreased CNS serotonin function is associated with a less favorable profile.

Update on one-lung ventilation: the use of continuous positive airway pressure ventilation and positive end-expiratory pressure ventilation--clinical application.

PURPOSE OF REVIEW: The purpose of this review is to examine the evidence for and the clinical use of continuous positive airway pressure (CPAP) and positive end-expiratory pressure (PEEP) for the management of one-lung ventilation during thoracic surgery. CPAP and PEEP use are important as we are increasingly challenged with patients with less respiratory reserve and greater comorbidity leading to the need for greater clinical management and more interventions during one-lung ventilation for thoracic surgery to prevent perioperative complications. RECENT FINDINGS: The focus of this article is on the most recent literature with selected classic articles. First, the supportive literature and rationale for application of PEEP, CPAP or both during thoracic surgery are reviewed, relative to the threats of hypoxemia, hyperoxia and mechanical lung injury. The second part of the article focuses on the clinical use of PEEP and CPAP. Algorithms for the application of CPAP and PEEP to patients both at risk and not at risk of acute lung injury are presented. SUMMARY: CPAP and PEEP are useful not only to treat hypoxia and atelectasis as the consequence of one-lung ventilation, perhaps more importantly, also as part of a protective lung-ventilation strategy to ameliorate mechanical stress and prevent acute lung injury.

A bibliometric analysis of global clinical research by anesthesia departments.

BACKGROUND: Few studies have investigated the diversity in research conducted by anesthesia-based researchers. We examined global clinical research attributed to anesthesia departments using Medline and Ovid databases. We also investigated the impact of economic development on national academic productivity. METHODS: We conducted a Medline search for English-language publications from 2000 to 2005. The search included only clinical research in which institutional affiliation included words relating to anesthesia (e.g., anesthesiology, anesthesia, etc.). Population and gross national income data were obtained from publicly available databases. Impact factors for journals were obtained from Journal Citation Reports (Thomson Scientific). RESULTS: There were 6736 publications from 64 countries in 551 journals. About 85% of all publications were represented by 46 journals. Randomized controlled trials constituted 4685 (70%) of publications. Turkey had the highest percentage of randomized controlled trials (88%). The United States led the field in quantity (20% of total) and mean impact factor (3.0) of publications. Finland had the highest productivity when adjusted for population (36 publications per million population). Publications from the United States declined from 23% in 2000 to 17% in 2005. CONCLUSIONS: Clinical research attributable to investigators in our specialty is diverse, and extends beyond the traditional field of anesthesia and intensive care. The United States produces the most clinical research, but per capita output is higher in European nations.

Prevalence of difficult intubation and failed intubation in a diverse obstetric community-based population.

OBJECTIVE: To describe the incidence of difficult and failed intubations in obstetric patients during a 6 year period monitored by a quality assurance program together with American Society of Anesthesiologists Physical Status (ASA PS) scores, and obesity (body mass index >30 kg/m2). METHODS: Following Institutional Review Board approval, data about obstetric patients who experienced unanticipated difficult or failed intubations from 2010 to 2015 was obtained from the quality assurance database of a large, community-based anesthesiology group practice. The database employs standardized definitions for difficult intubation (>3 laryngoscopic attempts by experienced providers) and failed intubation (inability to intubate leading to surgical airway or waking up the patient). ASA PS scores and comorbidities were also identified for obstetric general anesthetics using an internally developed quality assurance program, Quantum Clinical Navigation System. RESULTS: There were 2802 obstetric general anesthetics in the database of which 1085 (38.7%) were deemed as emergencies. There were no cases of failed intubation and seven cases of unanticipated difficult intubations (1:400 cases, 0.25% of all obstetric general anesthetics, 95% confidence interval 0.1-0.5%), six of which occurred during emergency surgery. There was an increase in obesity (p = .003) and ASA PS (p = .02) over the period of the study. The incidence of difficult intubation was not found to be significantly changed (p = .68). CONCLUSIONS: Despite an increase in ASA PS score and obesity, there was no increase in the incidence of difficult intubation in obstetric patients. Limitations of the study include its retrospective design, and the small number of difficult intubation cases identified.

Associations between ASA Physical Status and postoperative mortality at 48 h: a contemporary dataset analysis compared to a historical cohort.

BACKGROUND: In this study, we examined the association between American Society of Anesthesiologists Physical Status (ASA PS) designation and 48-h mortality for both elective and emergent procedures in a large contemporary dataset (patient encounters between 2009 and 2014) and compared this association with data from a landmark study published by Vacanti et al. in 1970. METHODS: Patient history, hospital characteristics, anesthetic approach, surgical procedure, efficiency and quality indicators, and patient outcomes were prospectively collected for 732,704 consecutive patient encounters between January 1, 2009, and December 31, 2014, at 233 anesthetizing locations across 19 facilities in two US states and stored in the Quantum™ Clinical Navigation System (QCNS) database. The outcome (death within 48 h of procedure) was tabulated against ASA PS designations separately for patients with and without "E" status labels. To maintain consistency with the historical cohort from the landmark study performed by Vacanti et al. on adult men at US naval hospitals in 1970, we then created a comparison cohort in the contemporary dataset that consisted of 242,103 adult male patients (with/without E designations) undergoing elective and emergent procedures. Differences in the relationship between ASA PS and 48-h mortality in the historical and contemporary cohorts were assessed for patients undergoing elective and emergent procedures. RESULTS: As reported nearly five decades ago, we found a significant trend toward increased mortality with increasing ASA PS for patients undergoing both elective and emergent procedures in a large contemporary cohort (p < 0.0001). Additionally, the overall mortality rate at 48 h was significantly higher among patients undergoing emergent compared to elective procedures in the large contemporary cohort (1.27 versus 0.03 %, p < 0.0001). In the comparative analysis with the historical cohort that focused on adult males, we found the overall 48-h mortality rate was significantly lower among patients undergoing elective procedures in the contemporary cohort (0.05 % now versus 0.24 % in 1970, p < 0.0001) but not significantly lower among those undergoing emergent procedures (1.88 % now versus 1.22 % in 1970, p < 0.0001). CONCLUSIONS: The association between increasing ASA PS designation (1-5) and mortality within 48 h of surgery is significant for patients undergoing both elective and emergent procedures in a contemporary dataset consisting of over 700,000 patient encounters. Emergency surgery was associated with a higher risk of patient death within 48 h of surgery in this contemporary dataset. These data trends are similar to those observed nearly five decades ago in a landmark study evaluating the association between ASA PS and 48-h surgical mortality on adult men at US naval hospitals. When a comparison cohort was created from the contemporary dataset and compared to this landmark historical cohort, the absolute 48-h mortality rate was significantly lower in the contemporary cohort for elective procedures but not significantly lower for emergency procedures. The underlying implications of these findings remain to be determined.

Pathophysiology and management of one-lung ventilation.

The ability to manage OLV effectively in patients with significant pulmonary disease is increasing. Knowledge of pulmonary ventilation and perfusion physiology, improvements in the ability to prevent and treat hypoxia, and a thorough grasp of traditional and novel ventilatory techniques may promote improved perioperative outcomes.

Serotonin-related gene polymorphisms and central nervous system serotonin function.

Central nervous system (CNS) serotonergic function affects a wide range of biological and behavioral functions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnover-indexed by cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)-in a community sample of healthy adults. Subjects were 165 community volunteers without current medical or psychiatric illness, stratified with respect to ethnicity, gender, and socioeconomic status who underwent inpatient evaluation in the General Clinical Research Center of a university medical center. A significant ethnicity x genotype interaction (P=0.008) indicated that, compared to the long/long and long/short genotypes, the 5HTTLPR short/short genotype was associated with higher CSF 5-HIAA levels in African Americans, but with lower levels in Caucasians. A gender x genotype interaction (P=0.04) indicated that 5HTTLPR short/short genotype was associated with higher 5-HIAA levels in women but with lower levels in men. MAOA-uVNTR 3.5 and 4 repeat alleles were associated with higher 5-HIAA (P=0.03) levels in men, but were unrelated to 5-HIAA levels in women. These findings suggest that effects of serotonin-related gene polymorphisms on CNS serotonergic function vary as a function of both ethnicity and gender. Further research will be required to determine the mechanism(s) underlying these differential effects. In the meanwhile, both ethnicity and gender should be taken into account in research evaluating effects of these and related polymorphisms on CNS serotonergic function, as well as the broad range of biological and behavioral functions that are regulated by CNS serotonergic function.

Acute lung injury and acute respiratory distress syndrome after pulmonary resection.

The occurrence of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) after thoracic surgery are perplexing and persistent problems. Variously described as postpneumonectomy pulmonary edema, noncardiogenic pulmonary edema, and postlung resection pulmonary edema, ALI and ARDS may be considered a single entity, with ALI being the less severe form of ARDS. It is characterized by the acute onset of hypoxemia with radiographic infiltrates consistent with pulmonary edema, without elevations in the pulmonary capillary wedge pressure. Although this syndrome does not occur frequently and is usually without identifiable cause, the mortality is high. However, the phenomenon has not been rigorously studied owing to the low incidence, with primarily retrospective case series reported. Thus, the nomenclature, risks, and pathogenesis are not well defined. Interest in this syndrome has recently been renewed as the rate of other perioperative complications has declined. ALI/ARDS is reviewed with a focus on potential etiologies and the spectrum of available interventions.

Preoperative evaluation of the vascular surgery patient.

Patients undergoing vascular surgery present a myriad of perioperative challenges due to the complex comorbidities affecting them in conjunction with high-risk surgical procedures. Additionally, advances in endovascular technology have enabled surgical procedures to be performed on patients who would not have been considered surgical candidates in the past. This combination of increasing patient morbidity and evolving surgical technique requires a well-planned preoperative assessment and close communication with surgical and perioperative colleagues. This article outlines an appropriate approach by first considering each organ system, followed by review of considerations unique to various surgical procedures, and then an overall assessment of risk.

Preoperative CYP2D6 metabolism-dependent ß-blocker use and mortality after coronary artery bypass grafting surgery.

OBJECTIVE: Recently, the role of ß-blockers (BBs) in reducing perioperative mortality has been challenged. The conflicting results might have resulted from the extent of BB metabolism by the cytochrome P-450 (CYP2D6) isoenzyme. The purpose of the present study was to assess the association between the preoperative use of BBs dependent on metabolism of the CYP2D6 isoenzyme with operative mortality after coronary artery bypass grafting surgery. METHODS: We performed a retrospective study of 5248 patients who had undergone coronary bypass grafting surgery from January 1, 2001 to November 30, 2009 at Duke University Medical Center. The cohorts were defined by the preoperative use of BBs and BB type (non-CYP2D6_BBs, CYP2D6_BBs, or no BBs). Operative mortality was analyzed using inverse probability-weighted estimators with propensity score adjustment. RESULTS: Of the 5248 patients, 14% received non-CYP2D6_BBs, 43%, CYP2D6_BBs, and 43%, no BBs. The incidence of operative mortality was 0.8%, 2.1%, and 3.7% in the non-CYP2D6_BB, CYP2D6_BB, and no BB groups, respectively. Multivariable inverse probability-weighted-adjusted analyses showed that non-CYP2D6_BBs were associated with a lower incidence of operative mortality (odds ratio, 0.33; 95% confidence interval, 0.13-0.83; P = .02) compared with no BB use and a trend toward lower operative mortality (odds ratio, 0.44; 95% confidence interval, 0.16-1.07; P = .06) compared with CYP2D6_BBs. No significant decrease occurred in the risk of operative mortality between the CYP2D6_BB and no BB groups (odds ratio, 0.85; 95% confidence interval, 0.54-1.34; P = .48). CONCLUSIONS: Among these patients, preoperative non-CYP2D6_BB use, but not CYP2D6_BB use, was associated with a decreased risk of operative mortality.

VISION: a regional performance improvement initiative for HIV health care providers.

INTRODUCTION: VISION (HIV Integrated Learning ModuleS: Achieving Performance Improvement through CollaboratiON) was a regional performance improvement (PI) continuing medical education (CME) initiative designed to increase guideline-conforming practice of clinicians who manage patients with HIV infection. METHODS: The 3-part activity consisted of (1) clinical practice assessment and development of an action plan for practice change, (2) completion of relevant education, and (3) reassessment. RESULTS: The activity did not change practitioners' performance in clinical status monitoring and in patient treatment, in large part because guidelines were being appropriately implemented at baseline as well as after the educational intervention. There was a trend toward improvement, however, in practitioner performance in the area of patient medication adherence (increased from 66% to 74%). DISCUSSION: Results observed in the VISION initiative were consistent with HIVQUAL metrics. Ongoing education in HIV is important, and VISION demonstrated performance improvement in medication adherence, a critical aspect of health care.