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Pharmacogenomics, which offers a potential means by which to inform prescribing and avoid adverse drug reactions, has gained increasing consideration in other medical settings but has not been broadly evaluated during perioperative care.The Implementation of Pharmacogenomic Decision Support in Surgery (ImPreSS) Trial is a prospective, single-center study consisting of a prerandomization pilot and a subsequent randomized phase. We describe findings from the pilot period. Patients planning elective surgeries were genotyped with pharmacogenomic results, and decision support was made available to anesthesia providers in advance of surgery. Pharmacogenomic result access and prescribing records were analyzed. Surveys (Likert-scale) were administered to providers to understand utilization barriers.Of eligible anesthesiology providers, 166 of 211 (79%) enrolled. A total of 71 patients underwent genotyping and surgery (median, 62 years; 55% female; average American Society of Anesthesiologists (ASA) score, 2.6; 58 inpatients and 13 ambulatories). No patients required postoperative intensive care or pain consultations. At least 1 provider accessed pharmacogenomic results before or during 41 of 71 surgeries (58%). Faculty were more likely to access results (78%) compared to house staff (41%; P = .003) and midlevel practitioners (15%) ( P.0001). Notably, all administered intraoperative medications had favorable genomic results with the exception of succinylcholine administration to 1 patient with genomically increased risk for prolonged apnea (without adverse outcome). Considering composite prescribing in preoperative, recovery, throughout hospitalization, and at discharge, each patient was prescribed a median of 35 (range 15-83) total medications, 7 (range 1-22) of which had annotated pharmacogenomic results. Of 2371 prescribing events, 5 genomically high-risk medications were administered (all tramadol or omeprazole; with 2 of 5 pharmacogenomic results accessed), and 100 genomically cautionary mediations were administered (hydralazine, oxycodone, and pantoprazole; 61% rate of accessing results). Providers reported that although results were generally easy to access and understand, the most common reason for not considering results was because remembering to access pharmacogenomic information was not yet a part of their normal clinical workflow.Our pilot data for result access rates suggest interest in pharmacogenomics by anesthesia providers, even if opportunities to alter prescribing in response to high-risk genotypes were infrequent. This pilot phase has also uncovered unique considerations for implementing pharmacogenomic information in the perioperative care setting, and new strategies including adding the involvement of surgery teams, targeting patients likely to need intensive care and dedicated pain care, and embedding pharmacists within rounding models will be incorporated in the follow-on randomized phase to increase engagement and likelihood of affecting prescribing decisions and clinical outcomes.

Patients with a history of hypertensive disorders of pregnancy (HDP) suffer higher rates of long-term cardiovascular events including heart failure, coronary artery disease, and stroke. Cardiovascular changes during pregnancy can act as a natural stress test, subsequently unmasking latent cardiovascular disease in the form of HDP. Because HDP now affect 10% of pregnancies in the United States, the American Heart Association has called for physicians who provide peripartum care to promote early identification and cardiovascular risk reduction. In this review, we discuss the epidemiology, pathophysiology, and outcomes of HDP-associated cardiovascular disease. In addition, we propose a multi-pronged approach to support cardiovascular risk reduction for women with a history of HDP. Additional research is warranted to define appropriate blood pressure targets in the postpartum period, optimize the use of pregnancy history in risk stratification tools, and clarify the effectiveness of preventive interventions. The highest rates of HDP are in populations with poor access to resources and quality health care, making it a major risk for inequity of care. Interventions to decrease long-term cardiovascular disease risk in women following HDP must also target disparity reduction.

Background Anesthesia staffing models rely on predictable surgical case volumes. Previous studies have found no relationship between month of the year and surgical volume. However, seasonal events and greater use of high-deductible health insurance plans may cause U.S. patients to schedule elective surgery later in the calendar year. The hypothesis was that elective anesthesia caseloads would be higher in December than in other months. Methods This review analyzed yearly adult case data in Florida and Texas locations of a multistate anesthesia practice from 2017 to 2019. To focus on elective caseload, the study excluded obstetric, weekend, and holiday cases. Time trend decomposition analysis was used with seasonal variation to assess differences between December and other months in daily caseload and their relationship to age and insurance subgroups. Results A total of 3,504,394 adult cases were included in the analyses. Overall, daily caseloads increased by 2.5 ± 0.1 cases per day across the 3-yr data set. After adjusting for time trends, the average daily December caseload in 2017 was 5,039 cases (95% CI, 4,900 to 5,177), a 20% increase over the January-to-November baseline (4,196 cases; 95% CI, 4,158 to 4,235; P < 0.0001). This increase was replicated in 2018: 5,567 cases in December (95% CI, 5,434 to 5,700) versus 4,589 cases at baseline (95% CI, 4,538 to 4,641), a 21.3% increase; and in 2019: 6,103 cases in December (95% CI, 5,871 to 6,334) versus 5,045 cases at baseline (95% CI, 4,984 to 5,107), a 21% increase (both P < 0.001). The proportion of commercially insured patients and those aged 18 to 64 yr was also higher in December than in other months. Conclusions In this 3-yr retrospective analysis, it was observed that, after accounting for time trends, elective anesthesia caseloads were higher in December than in other months of the year. Proportions of commercially insured and younger patients were also higher in December. When compared to previous studies finding no increase, this pattern suggests a recent shift in elective surgical scheduling behavior. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background: Transcatheter pulmonic valve implantation (TPVI) is a minimally invasive procedure that treats patients with dysfunction of the pulmonic valve or right-ventricular-to-pulmonary artery c...

OBJECTIVES: Integration of pharmacogenomics into clinical care is being studied in multiple disciplines. We hypothesized that understanding attitudes and perceptions of anesthesiologists, critical care, and pain medicine providers would uncover unique considerations for future implementation within perioperative care. METHODS: A survey (multiple choice and Likert-scale) was administered to providers within our Department of Anesthesia and Critical Care prior to initiation of a department-wide prospective pharmacogenomics implementation program. The survey addressed knowledge, perceptions, experiences, resources, and barriers. RESULTS: Of 153 providers contacted, 149 (97%) completed the survey. Almost all providers (92%) said that genetic results influence drug therapy, and few (22%) were skeptical about the usefulness of pharmacogenomics. Despite this enthusiasm, 87% said their awareness about pharmacogenomic information is lacking. Feeling well-informed about pharmacogenomics was directly related to years in practice/experience: only 38% of trainees reported being well-informed, compared to 46% of those with 1–10 years of experience, and nearly two-thirds with 11+ years (p

ObjectivesTo evaluate the analytical and clinical performance of the Truvian Easy Check coronavirus disease 2019 (COVID-19) IgM/IgG anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody test.Serologic assays have become increasingly available for surveillance through the Food and Drug Administration emergency use authorization in the ongoing COVID-19 global pandemic. However, widespread application of serologic assays has been curbed by reports of faulty or inaccurate tests. Therefore, rapid COVID-19 antibody tests need to be thoroughly validated prior to their implementation.MethodsThe Easy Check device was analytically evaluated and its performance was compared with the Roche Elecsys anti-SARS-CoV-2 antibody assay. The test was further characterized for cross-reactivity using sera obtained from patients infected by other viruses. Clinical performance was analyzed with polymerase chain reaction-confirmed samples and a 2015 prepandemic reference sample set.ResultsThe Easy Check device showed excellent analytical performance and compares well with the Roche Elecsys antibody assay, with an overall concordance of 98.6%. Clinical performance showed a sensitivity of 96.6%, a specificity of 98.2%, and an overall accuracy of 98.1%.ConclusionsThe Easy Check device is a simple, reliable, and rapid test for detection of SARS-CoV-2 seropositivity, and its performance compares favorably against the automated Roche Elecsys antibody assay.

Study Objective: To identify risk factors for pediatric postoperative respiratory failure and develop a predictive model. Design: This retrospective case–control study utilized the US National Inpatient Sample (NIS) from 2012 to 2014. Significant predictors were selected, and the predicted probability of pediatric postoperative respiratory failure was calculated. Sensitivity, specificity, and accuracy were then calculated, and receiver–operator curves were drawn. Setting: National Inpatient Sample data sets from years 2012, 2013, and 2014 were used. Patients: Patients aged 17 and younger in the 2012, 2013, and 2014 NIS data sets. Interventions: Candidate predictors included demographic variables, type of surgical procedure, a modified pediatric comorbidity score, presence of substance abuse diagnosis, and presence/absence of kyphoscoliosis. Measurements: The primary outcome measure was the pediatric quality indicator (PDI 09), which is defined by the Agency for Healthcare Research Quality, and identifies pediatric patients with postoperative respiratory failure. Main Results: The incidence of pediatric postoperative respiratory failure in each year’s data set varied from 1.31% in 2012 to 1.41% in 2014. Significant risk factors for the development of postoperative respiratory failure included abdominal surgery ([OR] = 1.92 in 2012 data set, 1.79 in 2013 data set), spine surgery (OR = 7.10 in 2012 data set, 6.41 in 2013 data set), and an elevated pediatric comorbidity score (score of 3 or greater: OR = 32.58 in 2012 data set, 22.74 in 2013 data set). A predictive model utilizing these risk factors achieved a C statistic of 0.82. Conclusions: Risk factors associated with postoperative respiratory failure in pediatric patients undergoing noncardiac surgery include type of surgery (abdominal and spine) and higher pediatric comorbidity scores. A prediction model based on the identified factors had good predictive ability.

Objectives To systematically explore the relationship among the use of mechanical circulatory support (MCS), the timing of placement, and outcomes in pregnancy. Design Using the National Inpatient Sample and National Readmissions Database, the authors performed a retrospective, cohort analysis of peripartum women who received MCS. Setting United States hospitals. Participants A weighted sample of women who received MCS during the antepartum, delivery, or postpartum period between 2002 and 2014. Interventions MCS Measurements and Main Results There were 1,386 women who received MCS during their admission. These women were older and had more comorbidities than women without MCS. The mean time from admission to device placement was 5.4 days for all women, and MCS use was highest in urban teaching hospitals. Overall, peripartum use of MCS has increased since 2002, but mortality did not change during the same period. After adjusting for potential confounders, the odds ratio for mortality when MCS was placed within 6 days of admission was 0.48 (95% confidence interval 0.23-0.98) with the adjusted probability of death rising from 18.6% to 32.5% when the device was placed on or after day 6. Conclusions Similar to trends in the general population, use of MCS has increased in the peripartum period. Women receiving MCS were generally older and had more comorbidities than those not receiving MCS. Increased time to device placement may worsen mortality. Further research will help identify appropriate candidates and factors that improve survival.

Since the first recognition of a cluster of novel respiratory viral infections in China in late December 2019, intensivists in the United States have watched with growing concern as infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus―now named Coronavirus Disease of 2019 (COVID-19)―have spread to hospitals in the United States. Because COVID-19 is extremely transmissible and can progress to a severe form of respiratory failure, the potential to overwhelm available critical care resources is high and critical care management of COVID-19 patients has been thrust into the spotlight. COVID-19 arrived in the United States in January and, as anticipated, has dramatically increased the usage of critical care resources. Three of the hardest-hit cities have been Seattle, New York City, and Chicago with a combined total of over 14,000 cases as of March 23, 2020. In this special article, we describe initial clinical impressions of critical care of COVID-19 in these areas, with attention to clinical presentation, laboratory values, organ system effects, treatment strategies, and resource management. We highlight clinical observations that align with or differ from already published reports. These impressions represent only the early empiric experience of the authors and are not intended to serve as recommendations or guidelines for practice, but rather as a starting point for intensivists preparing to address COVID-19 when it arrives in their community.

Objective: Robotic totally endoscopic coronary bypass (R-TECAB) has been shown to be a safe and effective technique with excellent outcomes. The aim of this study is to assess the feasibility of R-TECAB in patients with low left ventricular ejection fraction (LVEF) and to report our midterm outcomes with up to 7-year follow-up. Methods: All patients undergoing R-TECAB at our institution between July 2013 and July 2020 were retrospectively reviewed. A total of 100 patients were identified with low LVEF defined as ≤40%. The preoperative characteristics, perioperative and postoperative outcomes, as well as the midterm results were reviewed. Results: The mean LVEF was 31%, and 62% of all patients had preexisting congestive heart failure. Of the cohort, 59% had 3-vessel disease and 6% underwent previous cardiac surgery. Multivessel TECAB was performed in 54%. Hybrid coronary revascularization occurred in 36 individuals. Two patients required cardiopulmonary bypass, and 35% were extubated in the operating room. No sternotomy conversions were required. One patient underwent reoperation for bleeding. No perioperative stroke, myocardial infarction, or mortality occurred. The left internal mammary artery graft patency was 97% at a mean of 1.6 months in the staged hybrid percutaneous coronary intervention group. At midterm follow-up the cardiac-related mortality was 5%. Heart transplant or left ventricular assist device was required in 4 patients, and 1 patient experienced a myocardial infarction. Freedom from major adverse cardiac events was 89%. Conclusions: Off-pump TECAB can be successfully performed in patients with low LVEF in the setting of an experienced and dedicated robotic cardiac surgery team. Our data demonstrate the feasibility of the technique with excellent perioperative and midterm outcomes.

Neuraxial labor analgesia is associated with elevations in maternal temperature; the mechanism responsible is unknown. Proposed mechanisms have included infection, altered thermoregulation, and inflammation, potentially triggered by local anesthetics. Studies of the association between neuraxial labor analgesia and maternal fever have focused on epidural analgesia, and there have been no comparisons of the rate of maternal fever between continuous spinal and epidural labor analgesia.We performed a retrospective study to compare the rate of maternal fever between patients who received continuous spinal versus epidural labor analgesia between June 2012 and March 2020. Each patient who received continuous spinal analgesia was matched to 2 patients who received epidural analgesia and had the same nulliparous status. The primary outcome of our study was the incidence of intrapartum maternal fever, which we defined as any temperature ≥38 °C before delivery and compared between the continuous spinal and epidural groups using Fisher exact test.We identified 81 patients who received continuous spinal analgesia and 162 matched controls who received epidural analgesia. Demographic and obstetric characteristics of the patients were similar between groups. While the duration of analgesia did not significantly differ, there was markedly increased bupivacaine consumption in women with epidural analgesia. Eight of 81 (9.9%; 95% confidence interval [CI], 5.1-18.3) women with continuous spinal analgesia developed an intrapartum fever compared to 18 of 162 (11.1%; 95% CI, 7.1-16.9) of women with epidural analgesia ( P = .83; Fisher exact test).There was no significant difference in the rate of maternal fever between women with continuous spinal compared to epidural labor analgesia. While the route of administration and dose of bupivacaine differs between epidural and spinal labor analgesia, they are titrated to produce similar levels of neuraxial blockade. Our results are consistent with a model in which epidural related maternal fever is due to altered thermoregulation from a central neuraxial block and argue against a direct effect of bupivacaine or fentanyl, although we cannot rule out a concentration-independent effect of bupivacaine or fentanyl or an inflammatory effect of the catheter itself. These retrospective results highlight the importance of prospective and mechanistic study of neuraxial analgesia-related maternal fever.

Introduction: Peripartum cardiomyopathy (PPCM) is a rare form of pregnancy-related heart failure associated with preeclampsia. Our understanding of their shared pathophysiology is limited as are treatment options. Hypothesis: We hypothesized that plasma proteomic profiling would identify deleterious circulating proteins and provide insights into shared mechanisms driving preeclampsia and PPCM. Methods: We performed serum proteomic case-control studies in women with preeclampsia or PPCM to identify biological processes common to both conditions. The top candidate was validated in independent preeclampsia (n=58) and PPCM (n=114) cohorts. Preeclamptic placenta was examined as a potential source of circulating proteins. Therapeutic targeting the top candidate was examined in an animal model of PPCM. Results: Paradoxically, we found the senescence-associated secretory phenotype (SASP), a marker of biological aging, to be the most upregulated process in relatively young women with preeclampsia (normalized enrichment score [NES]=3.3;p adj =4.0x10 -6 ) or PPCM (NES=3.2;p adj =1.9x10 -5 ). 28 circulating proteins contributed to this common signal, and were strongly enriched in preeclamptic placenta, which expressed markers of increased senescence. The TGFb family member, Activin-A, was the most highly upregulated SASP gene in preeclamptic placentas (5-fold;p Conclusions: These data implicate placental senescence in the increased deleterious circulating proteins seen in preeclampsia and PPCM. We identify multiple new circulating factors associated with these diseases and demonstrate that targeting SASP proteins, such as Activin-A, can mitigate PPCM in mice.

BACKGROUND. Preeclampsia (PE) is a disorder prevalent in 3–8% of pregnancies, characterized by hypertension, endothelial dysfunction and cardiac dysfunction, including hypertrophy and impaired global longitudinal strain (GLS), which indicates reduced contractility and tissue injury. Despite several clinical studies highlighting impaired cardiac function in these women, the underlying mechanisms have not been studied, in part, due to lack of an appropriate animal model. The Reduced Uterine Perfusion Pressure (RUPP) rat model produces a PE-like phenotype, including adverse cardiac remodeling. However, whether this translates to impaired cardiac function is not known. The aim of this study was to test the hypothesis that placental ischemia in the RUPP rat leads to impaired left ventricular (LV) systolic function and GLS. STUDY DESIGN. RUPP (n=10) rats underwent surgery to induce placental ischemia on gestational day (GD) 14. Sham (n=10) and RUPP rats had indwelling carotid catheters placed on GD 18, and blood pressure and echocardiography measurements were made on GD 19. RESULTS. The RUPP group exhibited increased mean arterial pressure compared to the Sham group (123±3 vs. 97±2 mmHg, P

We implemented a new policy at our institution where the responsibility for intensive care unit (ICU) patient transports to the operating room (OR) was changed from the anesthesia to the ICU service. We hypothesized that this approach would be associated with increased on-time starts and decreased turnover times.In the historical model, intubated patients or those on mechanical circulatory assistance (MCA) were transported by the anesthesia service to the OR ("pre-ICU Pickup"). In our new model, these patients are transported by the ICU service to the preoperative holding area (Pre-op) where care is transferred to the anesthesia service ("post-ICU Transfer"). If judged necessary by the ICU or anesthesia attending, the patient was transported by the anesthesia service ("post-ICU Pickup"). We retrospectively reviewed case tracking data for patients undergoing surgery before (January 2014 to May 2015) and after implementation (July 2016 to June 2017) of the new policy. The primary outcome was the proportion of elective, weekday first-case, on-time starts. To adjust for confounders including comorbidities and time trends, we performed a segmented logistic regression analysis assessing the effect of our intervention on the primary outcome. Secondary outcomes were turnover times and compliance with preoperative checklist documentation.We identified 95 first-start and 86 turnover cases in the pre-ICU Pickup, 70 first-start and 88 turnover cases in the post-ICU Transfer, and 6 turnover cases in the post-ICU Pickup group. Ignoring time trends, the crude proportion of on-time starts increased from 32.6% in the pre-ICU Pickup to 77.1% in the post-ICU Transfer group. After segmented logistic regression adjusting for age, sex, American Society of Anesthesiologists (ASA) physical status, Sequential Organ Failure Assessment (SOFA) score, respiratory failure, endotracheal intubation, MCA, congestive heart failure (CHF), valvular heart disease, and cardiogenic and hemorrhagic shock, the post-ICU Transfer group was more likely to have an on-time start at the start of the intervention than the pre-ICU Pickup group at the end of the preintervention period (odds ratio, 11.1; 95% confidence interval [CI], 1.3-125.7; P = .043). After segmented linear regression adjusting for the above confounders, the estimated difference in mean turnover times between the post-ICU Pickup and pre-ICU Transfer group was not significant (-6.9 minutes; 95% CI, -17.09 to 3.27; P = .17). In post-ICU Transfer patients, consent, history and physical examination (HP), and site marking were verified before leaving the ICU in 92.9%, 93.2%, and 89.2% of the cases, respectively. No adverse events were reported during the study period.A transition from the anesthesia to the ICU service for transporting ICU patients to the OR did not change turnover times but resulted in more on-time starts and high compliance with preoperative checklist documentation.

Objective Nondepolarizing neuromuscular blocking agents (NMBAs) are associated with perioperative complications in noncardiac surgery; however, little is known about their effect on cardiac surgery. This study assessed the effect of neuromuscular blockade (NMB) on the incidence of postoperative pulmonary complications (PPCs) after cardiac surgery and operating conditions. Design Prospective, randomized clinical trial with blinded outcomes assessment. Setting University hospital, single institution. Participants Adult patients having cardiac surgery requiring cardiopulmonary bypass. Interventions One hundred patients were randomized to receive succinylcholine (group SUX) for intubation with no further NMB administered or cisatracurium (group CIS) for intubation and maintenance NMB. The primary outcome was a composite incidence of PPCs in the 72 hours after elective cardiac surgery. PPCs included failure to extubate within 24 hours, need for reintubation, pneumonia, aspiration, unanticipated need for noninvasive respiratory support, acute respiratory distress, and mortality from respiratory arrest. The secondary outcome was the adequacy of operating conditions as assessed by blinded surgeon survey (including a rating of surgical conditions on a Likert scale from 1 = poor to 5 = excellent), anesthesiologist report, and patient questionnaire. Measurements and Main Results The composite incidence of PPCs did not differ between groups (8 of 50 patients in both groups; 16%). Mean surgeon rating of surgical conditions was lower in the SUX group (4.65 ± 0.85 v 4.96 ± 0.20, p = 0.02). Conclusion Although avoiding nondepolarizing NMBA is feasible, doing so worsened operating conditions and did not reduce the incidence of postoperative pulmonary complications.

Objective To study the association between hypertensive diseases of pregnancy and immediate postpartum development of heart failure in a large national database. Patients and Methods Using the 2013 to 2014 National Readmissions Database, which covered admissions from January 1 through September 30 in years 2013 and 2014, we examined 90-day readmission rates in parturients with a diagnosis of hypertensive disease of pregnancy who were discharged after delivery. The primary outcome was the association between the presence of hypertensive disease of pregnancy and readmission with heart failure within 90 days of delivery discharge. Secondary outcomes included readmission mortality, time between delivery discharge and readmission, length of stay, and costs of readmission. Results Women with hypertensive disease of pregnancy were more likely to be readmitted with heart failure (1809 of 25,908 readmissions (7.0%) vs 2622 of 89,660 readmissions (2.9%); P Conclusion Parturients with hypertensive disease of pregnancy were more likely to be readmitted with heart failure within 90 days of delivery. Most patients readmitted with heart failure were readmitted within 2 weeks of discharge after delivery. Patients readmitted with heart failure had substantial health care expenditures.

Background Preeclampsia is a prominent risk factor for long‐term development of cardiovascular disease. Although existing studies report a strong correlation between preeclampsia and heart failure, the underlying mechanisms are poorly understood. One possibility is the glycoprotein growth factor activin A. During pregnancy, elevated activin A levels are associated with impaired cardiac global longitudinal strain at 1 year, but whether these changes persist beyond 1 year is not known. We hypothesized that activin A levels would remain increased more than 1 year after a preeclamptic pregnancy and correlate with impaired cardiac function. Methods and Results To test our hypothesis, we performed echocardiograms and measured activin A levels in women approximately 10 years after an uncomplicated pregnancy (n=25) or a pregnancy complicated by preeclampsia (n=21). Compared with women with a previously normal pregnancy, women with preeclampsia had worse global longitudinal strain (−18.3% versus −21.3%, P =0.001), left ventricular posterior wall thickness (0.91 mm versus 0.80 mm, P =0.003), and interventricular septal thickness (0.96 mm versus 0.81 mm, P =0.0002). Women with preeclampsia also had higher levels of activin A (0.52 versus 0.37 ng/mL, P =0.02) and activin/follistatin‐like 3 ratio (0.03 versus 0.02, P =0.04). In a multivariable model, the relationship between activin A levels and worsening global longitudinal strain persisted after adjusting for age at enrollment, mean arterial pressure, race, and body mass index ( P =0.003). Conclusions Our findings suggest that both activin A levels and global longitudinal strain are elevated 10 years after a pregnancy complicated by preeclampsia. Future studies are needed to better understand the relationship between preeclampsia, activin A, and long‐term cardiac function.

Variable responses to medications complicates perioperative care. As a potential solution, we evaluated and synthesized pharmacogenomic evidence that may inform anesthesia and pain prescribing to identify clinically actionable drug/gene pairs. Clinical decision-support (CDS) summaries were developed and were evaluated using Appraisal of Guidelines for Research and Evaluation (AGREE) II. We found that 93/180 (51%) of commonly-used perioperative medications had some published pharmacogenomic information, with 18 having actionable evidence: celecoxib/diclofenac/flurbiprofen/ibuprofen/piroxicam/CYP2C9, codeine/oxycodone/tramadol CYP2D6, desflurane/enflurane/halothane/isoflurane/sevoflurane/succinylcholine/RYR1/CACNA1S, diazepam/CYP2C19, phenytoin/CYP2C9, succinylcholine/mivacurium/BCHE, and morphine/OPRM1. Novel CDS summaries were developed for these 18 medications. AGREE II mean ± standard deviation scores were high for Scope and Purpose (95.0 ± 2.8), Rigor of Development (93.2 ± 2.8), Clarity of Presentation (87.3 ± 3.0), and Applicability (86.5 ± 3.7) (maximum score = 100). Overall mean guideline quality score was 6.7 ± 0.2 (maximum score = 7). All summaries were recommended for clinical implementation. A critical mass of pharmacogenomic evidence exists for select medications commonly used in the perioperative setting, warranting prospective examination for clinical utility.

Preeclampsia (PE) is a disorder prevalent in 3-8% of pregnancies, characterized by maternal hypertension, endothelial dysfunction and impaired cardiac function. PE develops in response to impaired spiral artery remodeling, leading to poor perfusion of the placenta. The ischemic placenta releases anti-angiogenic and pro-inflammatory factors into the maternal circulation leading to widespread endothelial activation. Studies have also shown that PE women exhibit decreased cardiac global longitudinal strain (GLS), a sensitive measure of systolic function that indicates fibrosis and tissue injury. Importantly, GLS remains impaired postpartum, when blood pressure has returned to normal, suggesting that placental factors could play a role in the development of cardiac dysfunction in PE. A recent study showed Activin A, a pro-fibrotic factor that is released by the placenta, is increased during PE and is predictive of impaired GLS one year postpartum. PE is a multifaceted disease, and whether increased circulating Activin A alone induces cardiac dysfunction is not known. We hypothesized that chronic excess levels of Activin A during pregnancy induces cardiac dysfunction. To address this, rats were administered vehicle ( n =6) or Activin A ( n =6/group; A2, 1.9μg/day, A3, 3 μg/day, A4, 6μg/day) via osmotic pump on gestational day (GD) 14. All animals had an indwelling carotid catheter placed on GD 18, followed by a comprehensive echocardiography assessment and blood pressure measurement on GD19. Activin A infusion resulted in significant increases in circulating Activin A in all treated groups (Vehicle, 585±47 pg/mL, A2, 2022±695 pg/mL, A3, 2511±409 pg/mL, A4, 2801±410 pg/mL, P

Background Approximately 60% of women have Stage B heart failure 1 year after a preeclamptic delivery. Emerging evidence suggests that the profibrotic growth factor activin A, which has been shown to induce cardiac fibrosis and hypertrophy, is elevated in preeclampsia and may be inhibited by aspirin therapy. We hypothesized that preeclamptic women receiving aspirin would have lower activin A levels and reduced global longitudinal strain ( GLS ), a sensitive measure of cardiac dysfunction, than women who do not receive aspirin. To test our hypothesis, we performed a cohort study of women with preeclampsia or superimposed preeclampsia and compared activin A levels and GLS in parturients who did or did not receive aspirin. Methods and Results Ninety‐two parturients were enrolled, of whom 25 (27%) received aspirin (81 mg/day) therapy. GLS , plasma activin A, and follistatin, which inactivates activin A, were measured. Women receiving aspirin therapy had lower median (interquartile range) levels of activin A (8.17 [3.70, 10.36] versus 12.77 [8.37, 31.25] ng/mL; P =0.001) and lower activin/follistatin ratio (0.59 [0.31, 0.93] versus 1.01 [0.64, 2.60] P =0.002) than women who did not receive aspirin, which also remained significant after multivariable analysis. Furthermore, GLS was worse in patients who did not receive aspirin (−19.84±2.50 versus −17.77±2.60%; P =0.03) despite no differences in blood pressure between groups. Conclusions Our study suggests that antepartum aspirin therapy reduced serum activin A levels and improved GLS in preeclamptic patients, suggesting that aspirin may mitigate the postpartum cardiac dysfunction seen in women with preeclampsia.

Background Wellness among resident physicians is important to their well-being and ability to provide clinical care. The relationship between physical activity and wellness among anesthesia residents has not yet been evaluated. We surveyed anesthesia residents to evaluate their levels of physical activity and self-perceived wellness scores. We hypothesized that residents with high self-reported physical activity levels would be more likely to have higher wellness scores. Methods Three hundred and twenty-three anesthesia residents were invited to participate in this cross-sectional survey study. The survey included questions regarding demographics (age, gender, clinical anesthesia year, work hours), physical activity (based off the US Department of Health and Human Services [USDHHS] guidelines), and wellness (using the Satisfaction With Life Scale). The relationship between wellness and physical activity levels was evaluated. Results One hundred forty-one residents responded (43.6% response rate). Thirty-eight (27.1%) residents met our activity threshold for physically active. Eighty-six respondents (61.4%) were classified as having high wellness based on their survey answers. No significant associations were found between demographic data and wellness, including age or clinical anesthesia training year. Among those residents who described physical activity consistent with USDHHS guidelines, 29 (76.3%) had high wellness scores. After logistic regression analysis, residents who achieved the physical activity guidelines were more likely to have high wellness scores (odds ratio 2.54, 95% confidence interval 1.13-6.20, P value .03). Conclusions Anesthesia resident physicians with high physical activity levels had higher self-perceived wellness scores.

Women with hypertensive disorders of pregnancy have an increased risk of subsequent heart failure and cardiovascular disease when compared with women with normotensive pregnancies. Although the mechanisms underlying these findings are unclear, elevated levels of the biomarker activin A are associated with myocardial dysfunction and may have predictive value. We hypothesized that elevated levels of antepartum activin A levels would correlate with postpartum cardiac dysfunction in women with hypertensive disorders of pregnancy. We prospectively studied 85 women to determine whether increased antepartum activin A levels were associated with cardiac dysfunction at 1 year postpartum as measured by global longitudinal strain. Thirty-two patients were diagnosed with preeclampsia, 28 were diagnosed with gestational or chronic hypertension, and the remainder were nonhypertensive controls. Activin A levels were measured with ELISA both in the third antepartum trimester and at 1 year postpartum. Comprehensive echocardiograms including measurement of global longitudinal strain were also performed at enrollment and at 1 year postpartum. Antepartum activin A levels correlated with worsening antepartum global longitudinal strain ( r =0.70; P =0.0001). Across the entire cohort, elevated antepartum activin A levels were associated with the development of abnormal global longitudinal strain at 1 year (C statistic 0.74; P =0.004). This association remained significant after multivariable adjustment for clinically relevant confounders (C statistic 0.93; P =0.01). Postpartum activin A levels also correlated with increasing left ventricular mass index ( P =0.02), increasing mean arterial pressures ( P =0.02), and decreasing E′ values ( P =0.01). Activin A may be a useful tool for identifying and monitoring patients at risk for postpartum development of cardiovascular disease.

BackgroundAlthough opioids remain the standard therapy for the treatment of postoperative pain, the prevalence of opioid misuse is rising. The extent to which opioid abuse or dependence affects readmission rates and healthcare utilization is not fully understood. It was hypothesized that surgical patients with a history of opioid abuse or dependence would have higher readmission rates and healthcare utilization.MethodsA retrospective cohort analysis was performed of patients undergoing major operating room procedures in 2013 and 2014 using the National Readmission Database. Patients with opioid abuse or dependence were identified using International Classification of Diseases codes. The primary outcome was 30-day hospital readmission rate. Secondary outcomes included hospital length of stay and estimated hospital costs.ResultsAmong the 16,016,842 patients who had a major operating room procedure whose death status was known, 94,903 (0.6%) had diagnoses of opioid abuse or dependence. After adjustment for potential confounders, patients with opioid abuse or dependence had higher 30-day readmission rates (11.1% vs. 9.1%; odds ratio 1.26; 95% CI, 1.22 to 1.30), longer mean hospital length of stay at initial admission (6 vs. 4 days; P < 0.0001), and higher estimated hospital costs during initial admission ($18,528 vs. $16,617; P < 0.0001). Length of stay was also higher at readmission (6 days vs. 5 days; P < 0.0001). Readmissions for infection (27.0% vs. 18.9%; P < 0.0001), opioid overdose (1.0% vs. 0.1%; P < 0.0001), and acute pain (1.0% vs. 0.5%; P < 0.0001) were more common in patients with opioid abuse or dependence.ConclusionsOpioid abuse and dependence are associated with increased readmission rates and healthcare utilization after surgery.

Sepsis and septic shock are prevalent conditions that are likely to increase in prevalence in the future. Given the high mortality and morbidity associated with sepsis and sepsis-induced cardiac dysfunction, we must continue to make advances in knowledge of the complex physiologic interactions and how we may target specific mediators for potential therapeutic options in the future.Multiple biomarkers have been discovered, which when assayed in sepsis-induced cardiomyopathy predict morbidity and mortality. With increased sensitivity of echocardiography, we can diagnose subclinical cardiac dysfunction, which may have future implications for slowing or preventing progressive dysfunction.Sepsis-induced cardiomyopathy is the result of complicated interactions between the pathogen, the body's response to infection, and iatrogenic injury. Interplay between inflammatory, metabolic, and adrenergic systems results in direct and indirect myocardial injury leading to decreases in both systolic and diastolic cardiac function. As the interactions are further elucidated with additional research into other proteins and mediators, new treatment options can be researched. VIDEO ABSTRACT.

To describe, with an emphasis on clinical applications, what is known about the pathophysiology, management, and implications of septic cardiomyopathy in the adult ICU.A PubMed literature review was performed for relevant articles. Only articles in English that studied human adults with sepsis were included.Multiple competing definitions for septic cardiomyopathy hinder understanding of this entity. Although many patients with sepsis develop cardiac dysfunction, the impact of septic cardiomyopathy on prognosis and therapy remains to be demonstrated. Treatment of septic cardiomyopathy is aimed at treating the underlying sepsis and providing specific supportive care for cardiogenic shock when present.Septic cardiomyopathy is an important contributor to organ dysfunction in sepsis. Guided treatment of septic cardiomyopathy may affect patients' prognosis, especially when their cardiac index is substantially decreased. The implication of septic cardiomyopathy for both short- and long-term outcomes is an important area for future investigation.

Background In some institutions, the current blood ordering practice does not discriminate minimally invasive endovascular aneurysm repair (EVAR) from open procedures, with consequent increasing costs and likelihood of blood product wastage for EVARs. This limitation in practice can possibly be addressed with the development of a reliable prediction model for transfusion risk in EVAR patients. We used the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database to create a model for prediction of intraoperative blood transfusion occurrence in patients undergoing EVAR. Afterward, we tested our predictive model on the Vascular Study Group of New England (VSGNE) database. Methods We used the ACS NSQIP database for patients who underwent EVAR from 2011 to 2013 (N = 4709) as our derivation set for identifying a risk index for predicting intraoperative blood transfusion. We then developed a clinical risk score and validated this model using patients who underwent EVAR from 2003 to 2014 in the VSGNE database (N = 4478). Results The transfusion rates were 8.4% and 6.1% for the ACS NSQIP (derivation set) and VSGNE (validation) databases, respectively. Hemoglobin concentration, American Society of Anesthesiologists class, age, and aneurysm diameter predicted blood transfusion in the derivation set. When it was applied on the validation set, our risk index demonstrated good discrimination in both the derivation and validation set (C statistic = 0.73 and 0.70, respectively) and calibration using the Hosmer-Lemeshow test ( P = .27 and 0.31) for both data sets. Conclusions We developed and validated a risk index for predicting the likelihood of intraoperative blood transfusion in EVAR patients. Implementation of this index may facilitate the blood management strategies specific for EVAR.

Chronic hypertension (cHTN) affects 7% of all pregnancies. We hypothesized that cHTN during pregnancy would be associated with abnormal myocardial strain patterns and adverse perinatal outcomes.This was a retrospective cohort study of patients seen in a high-risk obstetrics clinic with cHTN. Parturients with a singleton pregnancy who had undergone an echocardiogram as part of routine clinical care were eligible. Clinical and demographic information was collected from medical records. Global peak longitudinal strain (GLS) was measured using automated software from stored echocardiographic images.60 patients were included in this analysis, of which 48 (80.0%) were African American. The median BMI was 40.6, age was 34 years, and the gestational age was 20.4 weeks at the time of the echo and 37.9 weeks at delivery. Thirty-four patients (56.7%) demonstrated abnormal strain, defined as a GLS = -19%. Patients with abnormal strain were similar in age and BMI to patients with normal cardiac function. When compared to women with normal strain, those with abnormal strain had lower stroke volume (69.0 ml vs 81.5 ml; p = .001) and ejection fraction (49.6% vs 57.5%; p .0001). Rates of superimposed preeclampsia were higher (38.2% vs 11.5%, p-value = .02) and a higher proportion of patients in the abnormal strain group delivered before 37 weeks (44.1% vs 19.2%; p = .04).In a population of parturients with cHTN, we found that more than one-half demonstrated subclinical abnormal cardiac function. The presence of abnormal cardiac strain predates superimposed preeclampsia and preterm delivery. Further studies are needed to validate these findings.

Tachycardia is common in septic shock, but many patients with septic shock are relatively bradycardic. The prevalence, determinants, and implications of relative bradycardia (heart rate,80 beats/min) in septic shock are unknown. To determine mortality associated with patients who are relatively bradycardic while in septic shock.Retrospective study of patients admitted for septic shock to study ICUs during 2005-2013.One large academic referral hospital and two community hospitals.Adult patients with septic shock requiring vasopressors.None.Primary outcome was 28-day mortality. We used multivariate logistic regression to evaluate the association between relative bradycardia and mortality, controlling for confounding with inverse probability treatment weighting using a propensity score.We identified 1,554 patients with septic shock, of whom 686 (44%) met criteria for relative bradycardia at some time. Twenty-eight-day mortality in this group was 21% compared to 34% in the never-bradycardic group (p0.001). Relatively bradycardic patients were older (65 vs 60 yr; p0.001) and had slightly lower illness severity (Sequential Organ Failure Assessment, 10 vs 11; p = 0.004; and Acute Physiology and Chronic Health Evaluation II, 27 vs 28; p = 0.008). After inverse probability treatment weighting, covariates were balanced, and the association between relative bradycardia and survival persisted (p0.001).Relative bradycardia in patients with septic shock is associated with lower mortality, even after adjustment for confounding. Our data support expanded investigation into whether inducing relative bradycardia will benefit patients with septic shock.

Objective To study the association between hypertensive diseases of pregnancy and immediate postpartum development of heart failure in a large national database. Patients and Methods Using the 2013 to 2014 National Readmissions Database, which covered admissions from January 1 through September 30 in years 2013 and 2014, we examined 90-day readmission rates in parturients with a diagnosis of hypertensive disease of pregnancy who were discharged after delivery. The primary outcome was the association between the presence of hypertensive disease of pregnancy and readmission with heart failure within 90 days of delivery discharge. Secondary outcomes included readmission mortality, time between delivery discharge and readmission, length of stay, and costs of readmission. Results Women with hypertensive disease of pregnancy were more likely to be readmitted with heart failure (1809 of 25,908 readmissions (7.0%) vs 2622 of 89,660 readmissions (2.9%); P Conclusion Parturients with hypertensive disease of pregnancy were more likely to be readmitted with heart failure within 90 days of delivery. Most patients readmitted with heart failure were readmitted within 2 weeks of discharge after delivery. Patients readmitted with heart failure had substantial health care expenditures.

Preeclampsia (PE) is a disorder prevalent in 3-8% of pregnancies, characterized by maternal hypertension and endothelial dysfunction. More recently, it has been shown that preeclamptic women exhibit cardiac dysfunction, impaired global longitudinal strain (GLS), which is indicator of contractility and tissue injury, and increased circulating cardiac troponin I (cTnI), however the underlying mechanisms have not been well studied. The Reduced Uterine Perfusion Pressure (RUPP) model of placental ischemia mimics a PE-like phenotype, including hypertension, endothelial dysfunction and adverse cardiac remodeling. However, whether adverse remodeling translates to impaired cardiac function is not known. The aim of this study was to assess cardiac function in RUPP rats during pregnancy. We tested the hypothesis that placental ischemia in the RUPP rat leads to impaired left ventricular (LV) systolic function and GLS. To address this, all animals underwent comprehensive echocardiography assessment on gestational day (GD) 14. RUPP rats underwent surgery to place silver clips on the abdominal aorta and branches of the ovarian artery to induce placental ischemia. Both the Sham ( n =10) and RUPP ( n =10) rats had indwelling carotid catheters placed on GD 18, and blood pressure and echocardiography measurements were made on GD 19. The RUPP group showed significantly increased mean arterial pressure compared to the Sham group on GD 19 (123 ± 3 vs. 97 ± 2 mmHg, P

Several high-profile examples of adverse outcomes from medications used in the perioperative setting are well known (e.g., malignant hyperthermia, prolonged apnea, respiratory depression, inadequate analgesia), leading to an increased understanding of genetic susceptibilities underlying these risks. Pharmacogenomic information is increasingly being utilized in certain areas of medicine. Despite this, routine preoperative genetic screening to inform medication risk is not yet standard practice. In this review, we assess the current readiness of pharmacogenomic information for clinical consideration for several common perioperative medications, including description of key pharmacogenes, pharmacokinetic implications and potential clinical outcomes. The goal is to highlight medications for which emerging or considerable pharmacogenomic information exists and identify areas for future potential research.

Communication remains challenging to teach and evaluate. We designed an online patient survey to assess anesthesia residents' communication skills from August 2014 to July 2015. In December 2014, we implemented a customized, simulation-based curriculum. We calculated an overall rating for each survey by averaging the ratings for the individual questions. Based on the Hodges-Lehmann 2-sample aligned rank-sum test, overall ratings, reported as the median (interquartile range) of residents' average overall ratings, differed significantly between the preintervention (3.86 [3.76-3.94]) and postintervention (3.91 [3.84-3.95]) periods (P = .025). Future studies should assess the intervention's effectiveness and generalizability.

Cardiogenic shock (CS) may occur during pregnancy and dramatically worsen peripartum outcomes.We analyzed the National Inpatient Sample from 2002 to 2013 to describe the incidence of, risk factors for and outcomes of CS during pregnancy.Of the 53,794,192 hospitalizations analyzed, 2044 were complicated by CS. The mortality rate in peripartum women with CS was 18.81% versus 0.02% without. It occurs more often during postpartum (58.83%) as compared with delivery (23.47%) or antepartum (17.70%) hospitalizations. Factors associated with CS -related death included cardiac arrest, renal failure, and sepsis.CS during pregnancy occurs more commonly in the postpartum period and is associated with a high mortality.

The purpose of this position paper is to define the scope of perioperative ultrasound (US), review the current status of US training practices during anesthesiology residency, and suggest the recommendations for current and future trainees on how to obtain perioperative US proficiency. We define per

Hypertensive disorders of pregnancy (HDP) are associated with subclinical changes in cardiac function. Although the mechanism underlying this finding is unknown, elevated levels of soluble antiangiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng) are associated with myocardial dysfunction and may play a role. We hypothesized that these antiangiogenic proteins may contribute to the development of cardiac dysfunction in HDP. We prospectively studied 207 pregnant women with HDP and nonhypertensive controls and evaluated whether changes in global longitudinal strain (GLS) observed on echocardiography is specific for HDP and whether these changes correlate with HDP biomarkers, sFlt1 and sEng. A total of 62 (30%) patients were diagnosed with preeclampsia (group A), 105 (51%) did not have an HDP (group B), and 40 (19%) were diagnosed with chronic or gestational hypertension (group C). Blood was drawn and sFlt1 and sEng levels measured using enzyme-linked immunosorbent assay. Comprehensive echocardiograms, including measurement of GLS, were performed on all patients. Overall, GLS was worse in women in group A (preeclampsia) than those in group B or C. Increasing sFlt1 and sEng levels correlated with worsening GLS ( r =0.44 for sFlt1 and r =0.46 for sEng, both P r =0.18 and r =0.22, both P ≤0.01). Increasing levels also correlated with increasing left ventricular mass index, which also remained significant after multivariable analysis ( r =0.20 for sFlt1 and 0.19 for sEng, both P =0.01). Elevated circulating levels of antiangiogenic proteins in HDP correlate with and may contribute to myocardial dysfunction as measured by GLS.