Propofol-Based Anesthesia Maintenance and/or Volatile Anesthetics during Intracranial Aneurysm Repair: A Comparative Analysis of Neurological Outcomes.

BACKGROUND: Volatile and intravenous anesthetics have substantial effects on physiological functions, notably influencing neurological function and susceptibility to injury. Despite the importance of the anesthetic approach, data on its relative risks or benefits during surgical clipping or endovascular treatments for unruptured intracranial aneurysms (UIAs) remains scant. We investigated whether using volatile anesthetics alone or in combination with propofol infusion yields superior neurological outcomes following UIA obliteration. METHODS: We retrospectively reviewed 1001 patients who underwent open or endovascular treatment for UIA, of whom 596 had short- and long-term neurological outcome data (modified Rankin Scale) recorded. Multivariable ordinal regression analysis was performed to examine the association between the anesthetic approach and outcomes. RESULTS: Of 1001 patients, 765 received volatile anesthetics alone, while 236 received propofol infusion and volatile anesthetics (combined anesthetic group). Short-term neurological outcome data were available for 619 patients and long-term data for 596. No significant correlation was found between the anesthetic approach and neurologic outcomes, irrespective of the type of procedure (open craniotomy or endovascular treatment). The combined anesthetic group had a higher rate of ICU admission (p < 0.001) and longer ICU and hospital length of stay (LOS, p < 0.001). Similarly, a subgroup analysis revealed longer ICU and hospital LOS (p < 0.0001 and p < 0.001, respectively) in patients who underwent endovascular UIA obliteration under a combined anesthetic approach (n = 678). CONCLUSIONS: The addition of propofol to volatile anesthetics during UIA obliteration does not provide short- or long-term benefits to neurologic outcomes. Compared to volatile anesthetics alone, the combination of propofol and volatile anesthetics may be associated with an increased rate of ICU admission, as well as longer ICU and hospital LOS.

Just-in-Time In Situ Simulation Training as a Preparedness Measure for the Perioperative Care of COVID-19 Patients.

INTRODUCTION: Routine workflows were redesigned during the first surge of the COVID-19 pandemic to standardize perioperative management of patients and minimize the risk of viral exposure and transmission to staff members. Just-in-time (JIT), in situ simulation training was adopted to implement urgent change, the value of which in a public health crisis has not previously been explored. METHODS: Implementation of workflow changes in the setting of the COVID-19 pandemic was accomplished through JIT, in situ simulation training, delivered over a period of 3 weeks to participants from anesthesia, nursing, and surgery, within our healthcare network. The perceived value of this training method was assessed using a postsimulation training survey, composed of Likert scale assessments and free-text responses. The impact on change in practice was assessed by measuring compliance with new COVID-19 workflows for cases of confirmed or suspected COVID-19 managed in the operating room, between March and August 2020. RESULTS: Postsimulation survey responses collected from 110 of 428 participants (25.7%) demonstrated significant positive shifts along the Likert scale on perceived knowledge of new workflow processes, comfort in adopting them in practice and probability that training would have an impact on future practice (all P s < 0.001). Free-text responses reflected appreciation for the training being timely, hands-on, and interprofessional. Compliance with new COVID workflows protocols in practice was 95% (121 of 127 cases) and was associated with lower than expected healthcare worker test positive rates (<1%) within the network during this same period. CONCLUSIONS: These findings support JIT, in situ simulation training as a preparedness measure for the perioperative care of COVID-19 patients and demonstrate the value of this approach during public health crises.

Association Between Intraoperative Arterial Hypotension and Postoperative Delirium After Noncardiac Surgery: A Retrospective Multicenter Cohort Study.

BACKGROUND: It is unclear whether intraoperative arterial hypotension is associated with postoperative delirium. We hypothesized that intraoperative hypotension within a range frequently observed in clinical practice is associated with increased odds of delirium after surgery. METHODS: Adult noncardiac surgical patients undergoing general anesthesia at 2 academic medical centers between 2005 and 2017 were included in this retrospective cohort study. The primary exposure was intraoperative hypotension, defined as the cumulative duration of an intraoperative mean arterial pressure (MAP) <55 mm Hg, categorized into and short (<15 minutes; median [interquartile range {IQR}], 2 [1-4] minutes) and prolonged (≥15 minutes; median [IQR], 21 [17-31] minutes) durations of intraoperative hypotension. The primary outcome was a new diagnosis of delirium within 30 days after surgery. In secondary analyses, we assessed the association between a MAP decrease of >30% from baseline and postoperative delirium. Multivariable logistic regression adjusted for patient- and procedure-related factors, including demographics, comorbidities, and markers of procedural severity, was used. RESULTS: Among 316,717 included surgical patients, 2183 (0.7%) were diagnosed with delirium within 30 days after surgery; 41.7% and 2.6% of patients had a MAP <55 mm Hg for a short and a prolonged duration, respectively. A MAP <55 mm Hg was associated with postoperative delirium compared to no hypotension (short duration of MAP <55 mm Hg: adjusted odds ratio [ORadj], 1.22; 95% confidence interval [CI], 1.11-1.33; P < .001 and prolonged duration of MAP <55 mm Hg: ORadj, 1.57; 95% CI, 1.27-1.94; P < .001). Compared to a short duration of a MAP <55 mm Hg, a prolonged duration of a MAP <55 mm Hg was associated with greater odds of postoperative delirium (ORadj, 1.29; 95% CI, 1.05-1.58; P = .016). The association between intraoperative hypotension and postoperative delirium was duration-dependent (ORadj for every 10 cumulative minutes of MAP <55 mm Hg: 1.06; 95% CI, 1.02-1.09; P =.001) and magnified in patients who underwent surgeries of longer duration (P for interaction = .046; MAP <55 mm Hg versus no MAP <55 mm Hg in patients undergoing surgery of >3 hours: ORadj, 1.40; 95% CI, 1.23-1.61; P < .001). A MAP decrease of >30% from baseline was not associated with postoperative delirium compared to no hypotension, also when additionally adjusted for the cumulative duration of a MAP <55 mm Hg (short duration of MAP decrease >30%: ORadj, 1.13; 95% CI, 0.91-1.40; P = .262 and prolonged duration of MAP decrease >30%: ORadj, 1.19; 95% CI, 0.95-1.49; P = .141). CONCLUSIONS: In patients undergoing noncardiac surgery, a MAP <55 mm Hg was associated with a duration-dependent increase in odds of postoperative delirium. This association was magnified in patients who underwent surgery of long duration.

Effect of Intraoperative Arterial Hypotension on the Risk of Perioperative Stroke After Noncardiac Surgery: A Retrospective Multicenter Cohort Study.

BACKGROUND: Intraoperative cerebral blood flow is mainly determined by cerebral perfusion pressure and cerebral autoregulation of vasomotor tone. About 1% of patients undergoing noncardiac surgery develop ischemic stroke. We hypothesized that intraoperative hypotension within a range frequently observed in clinical practice is associated with an increased risk of perioperative ischemic stroke within 7 days after surgery. METHODS: Adult noncardiac surgical patients undergoing general anesthesia at Beth Israel Deaconess Medical Center and Massachusetts General Hospital between 2005 and 2017 were included in this retrospective cohort study. The primary exposure was intraoperative hypotension, defined as a decrease in mean arterial pressure (MAP) below 55 mm Hg, categorized into no intraoperative hypotension, short (<15 minutes, median [interquartile range {IQR}], 2 minutes [1-5 minutes]) and prolonged (≥15 minutes, median [IQR], 21 minutes [17-31 minutes]) durations. The primary outcome was a new diagnosis of early perioperative ischemic stroke within 7 days after surgery. In secondary analyses, we assessed the effect of a MAP decrease by >30% from baseline on perioperative stroke. Analyses were adjusted for the preoperative STRoke After Surgery (STRAS) prediction score, work relative value units, and duration of surgery. RESULTS: Among 358,391 included patients, a total of 1553 (0.4%) experienced an early perioperative ischemic stroke. About 42% and 3% of patients had a MAP of below 55 mm Hg for a short and a prolonged duration, and 49% and 29% had a MAP decrease by >30% from baseline for a short and a prolonged duration, respectively. In an adjusted analysis, neither a MAP <55 mm Hg (short duration: adjusted odds ratio [ORadj], 0.95; 95% confidence interval [CI], 0.85-1.07; P = .417 and prolonged duration: ORadj, 1.18; 95% CI, 0.91-1.55; P = .220) nor a MAP decrease >30% (short duration: ORadj, 0.97; 95% CI, 0.67-1.42; P = .883 and prolonged duration: ORadj, 1.30; 95% CI, 0.89-1.90; P = .176) was associated with early perioperative stroke. A high a priori stroke risk quantified based on preoperatively available risk factors (STRAS prediction score) was associated with longer intraoperative hypotension (adjusted incidence rate ratio, 1.04; 95% CI, 1.04-1.05; P < .001 per 5 points of the STRAS prediction score). CONCLUSIONS: This study found no evidence to conclude that intraoperative hypotension within the range studied was associated with early perioperative stroke within 7 days after surgery. These findings emphasize the importance of perioperative cerebral blood flow autoregulation to prevent ischemic stroke.

Anesthetic management of unruptured intracranial aneurysms: a qualitative systematic review.

Intracranial aneurysms (IA) occur in 3-5% of the general population and may require surgical or endovascular obliteration if the patient is symptomatic or has an increased risk of rupture. These procedures carry an inherent risk of neurological complications, and the outcome can be influenced by the physiological and pharmacological effects of the administered anesthetics. Despite the critical role of anesthetic agents, however, there are no current studies to systematically assess the intraoperative anesthetic risks, benefits, and outcome effects in this population. In this systematic review of the literature, we carefully examine the existing evidence on the risks and benefits of common anesthetic agents during IA obliteration, their physiological and clinical characteristics, and effects on neurological outcome. The initial search strategy captured a total of 287 published studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 28 studies were included in the final report. Our data showed that both volatile and intravenous anesthetics are commonly employed, without evidence that either is superior. Although no specific anesthetic regimens are promoted, their unique neurological, cardiovascular, and physiological properties may be critical to the outcome in vulnerable patients. In particular, patients at risk for perioperative ischemia may benefit from timely administration of anesthetic agents with neuroprotective properties and optimization of their physiological parameters. Further studies are warranted to examine if these anesthetic regimens can reduce the risk of neurological injury and improve the overall outcome in these patients.

Neurophysiologic Intraoperative Monitoring for Spine Surgery: A Practical Guide From Past to Present.

Intraoperative neuromonitoring was introduced in the second half of the 20th century with the goal of preventing patient morbidity for patients undergoing complex operations of the central and peripheral nervous system. Since its early use for scoliosis surgery, the growth and utilization of IOM techniques expanded dramatically over the past 50 years to include spinal tumor resection and evaluation of cerebral ischemia. The importance of IOM has been broadly acknowledged, and in 1989, the American Academy of Neurology (AAN) released a statement that the use of SSEPs should be standard-of-care during spine surgery. In 2012, both the AAN and the American Clinical Neurophysiology Society (ACNS) recommended that: "Intraoperative monitoring (IOM) using SSEPs and transcranial MEPs be established as an effective means of predicting an increased risk of adverse outcomes, such as paraparesis, paraplegia, and quadriplegia, in spinal surgery." With a multimodal approach that combines SSEPs, MEPs, and sEMG with tEMG and D waves, as appropriate, sensitivity and specificity can be maximized for the diagnosis of reversible insults to the spinal cord, nerve roots, and peripheral nerves. As with most patient safety efforts in the operating room, IOM requires contributions from and communication between a number of different teams. This comprehensive review of neuromonitoring techniques for surgery on the central and peripheral nervous system will highlight the technical, surgical and anesthesia factors required to optimize outcomes. In addition, this review will discuss important trouble shooting measures to be considered when managing ION changes concerning for potential injury.

Unplanned hospital admission after ambulatory surgery: a retrospective, single cohort study.

PURPOSE: We estimated the rate of unplanned hospital and intensive care unit (ICU) admissions following ambulatory surgery centre (ASC) procedures, and identified factors associated with their occurrence. METHODS: This retrospective cohort included adult patients who underwent ASC procedures within a large community practice from January 2010 to December 2014. Patients were categorized into two groups: unplanned postoperative hospital/ICU admission within 24 hr of procedure or uneventful discharge. Demographics, comorbidities, anesthesia type, procedure type, procedure group, and ASC facility were assessed. RESULTS: Of the 211,389 patients included, there were 211,147 uneventful discharges (99.89%) and 242 unplanned hospital admissions (0.11%), of which 75 were ICU admissions (0.04%). The multivariable logistic regression model for hospital admission showed an increased risk associated with age > 50 yr (odds ratio [OR], 1.53); American Society of Anesthesiologists (ASA) physical status (III vs II: OR, 1.45; IV vs II: OR, 1.88), comorbidity (chronic obstructive pulmonary disease: OR, 2.63; diabetes mellitus: OR, 1.62; transient ischemic attack: OR, 2.48) procedure (respiratory: OR, 2.92; digestive: OR, 2.66; musculoskeletal system: OR, 2.53), anesthetic management (general anesthesia [GA] and peripheral nerve block vs GA: OR, 1.79), and ASC facility (189BB: OR, 2.29; 30E9A: OR, 7.41; and BD21F: OR, 1.69). The multivariable logistic regression model for ICU admission showed increased risk of unplanned ICU admission associated with ASA physical status (ASA III vs II: OR, 3.0; ASA IV vs II: OR, 8.52), procedure (musculoskeletal system: OR, 2.45), and ASC facility (00E6C: OR, 3.14; 189BB: OR, 2.77; 30E9A: OR, 2.59; and BD21F: OR, 3.71). CONCLUSION: While a small percentage of adult patients who underwent ASC procedures required unplanned hospital admission (0.07%), approximately one-third of these admissions were to the ICU (0.04%). Facility was at least as strong a predictor of hospital admission as the patient- and/or procedure-specific variables.

RéSUMé: OBJECTIF: Nous avons estimé le taux d'admissions non planifiées à l'hôpital et à l'unité de soins intensifs (USI) après des interventions dans des centres de chirurgie ambulatoire (CCA), et identifié les facteurs associés à leur survenue. MéTHODE: Cette étude de cohorte rétrospective a porté sur des patients adultes ayant subi une intervention dans un CCA appartenant à une grande pratique communautaire entre janvier 2010 et décembre 2014. Les patients ont été catégorisés en deux groupes : admission postopératoire non planifiée à l'hôpital/USI dans les 24 h suivant l'intervention ou congé sans incident. Les données démographiques, les comorbidités, le type d'anesthésie, le type d'intervention, le groupe d'intervention et l'établissement de CCA ont été évalués. RéSULTATS: Parmi les 211 389 patients inclus, il y a eu 211 147 congés sans incident (99,89 %) et 242 admissions non planifiées à l'hôpital (0,11 %), 75 desquelles étaient des admissions à l'USI (0,04 %). Le modèle de régression logistique multivariée des admissions hospitalières a montré un risque accru associé à un âge > 50 ans (rapport de cotes [RC], 1,53); au statut physique ASA (American Society of Anesthesiologists) (III vs II : RC, 1,45; IV vs II : RC, 1,88), aux comorbidités (maladie pulmonaire obstructive chronique : RC, 2,63; diabète: RC, 1,62; accident ischémique transitoire : RC, 2,48); à l'intervention (respiratoire : RC, 2,92; digestive : RC, 2,66; appareil locomoteur : RC, 2,53); à la prise en charge anesthésique (anesthésie générale [AG] et bloc nerveux périphérique vs AG : RC, 1,79) et établissement de CCA (189BB : RC, 2,29; 30E9A : RC, 7,41; et BD21F : RC, 1,69). Le modèle de régression logistique multivariée des admissions à l'USI a montré un risque accru d'admission non planifiée à l'USI associé au statut physique ASA (ASA III vs II: RC, 3,0; ASA IV vs II: RC, 8,52), à l'intervention (appareil locomoteur : RC, 2,45), et à l'établissement de CCA (00E6C: RC, 3,14; 189BB: RC, 2,77; 30E9A: RC, 2,59; et BD21F: RC, 3,71). CONCLUSION: Alors qu'un faible pourcentage de patients adultes ayant subi des interventions en CCA ont nécessité une admission non planifiée à l'hôpital (0,11 %), environ un tiers de ces admissions étaient à l'USI (0,04 %). L'établissement était un prédicteur au moins aussi puissant d'admission à l'hôpital que les variables spécifiques au patient et/ou à l'intervention.

Delayed gastrointestinal-associated lymphoid tissue reconstitution in duodenum compared with rectum in HIV-infected patients initiating antiretroviral therapy.

BACKGROUND: We aimed to characterize the impact of antiretroviral therapy (ART) initiation on gastrointestinal-associated lymphoid tissue at various sites along the gastrointestinal site. METHODOLOGY: Peripheral blood and duodenal and rectal biopsies were obtained from 12 HIV to 33 treatment-naive HIV participants at baseline and after 9 months ART. Tissue was digested for immunophenotyping. Inflammatory, bacterial translocation and intestinal damage markers were measured in plasma. RESULTS: Twenty-six HIV patients completed follow-up. The lowest reconstitution of CD4 T cells and the lowest CD4/CD8 ratio during ART compared with blood were observed in the duodenum with the rectum being either intermediate or approaching blood levels. Regulatory T cells were in higher proportions in the duodenum than the rectum and neither declined significantly during ART. Several correlations with biomarkers of microbial translocation were observed including increases in lipoteichoic acid levels, which reflects Gram-positive bacterial translocation, correlated with increases in %CD4 T cells in the duodenum (Rho 0.773, P = 0.033), and with decreases in duodenal regulatory T-cell populations (Rho -0.40, P = 0.045). CONCLUSION: HIV-mediated immunological disruption is greater in the duodenum than rectum and blood before and during ART. Small intestine damage may represent a unique environment for T-cell depletion, which might be attenuated by interaction with Gram-positive bacteria.

Effect of baseline micronutrient and inflammation status on CD4 recovery post-cART initiation in the multinational PEARLS trial.

BACKGROUND & AIMS: Nutritional deficiency and inflammation may impact CD4+ T cell recovery during combination antiretroviral therapy (cART), particularly in resource-limited settings where malnutrition is prevalent. The aim of this study was to investigate the relationship of micronutrient and inflammation biomarkers to CD4 recovery after cART initiation. METHODS: We conducted a secondary analysis of a random sub-cohort sample (n = 270) from a multinational randomized trial of cART regimen efficacy among 1571 cART-naïve adults. We measured pre-cART serum levels of micronutrients (Vitamin A, B6, B12, D, total carotenoids, selenium, and iron) and inflammation (C-reactive protein, soluble CD14 (sCD14), IFNγ, TNFα, Interleukin-6, and C-X-C motif chemokine 10 (CXCL10/IP10), EndoCab (IgM)) biomarkers. Biomarker status (i.e. micronutrient deficiency vs. sufficiency and elevated vs. low inflammation) was defined using established cutoffs or quartiles. Mixed-effects linear regression models were used to determine the association of baseline (pre-cART) concentrations of individual biomarkers with CD4 recovery through 96 weeks post-cART initiation. RESULTS: In models adjusting for time-dependent viral load and baseline CD4 count, age, sex, body mass index, country, treatment regimen, anemia and hypoalbuminemia status, pre-cART vitamin D deficiency was associated with lower CD4 recovery (-14.9 cells/mm3, 95% CI: -27.9, -1.8) compared to sufficiency. In contrast, baseline selenium deficiency (20.8 cells/mm3, 95% CI: 3.3, 38.3), vitamin A deficiency (35.9 cells/mm3, 95% CI: 17.6, 54.3) and high sCD14 (23.4 cells/mm3, 95% CI: 8.9, 37.8) were associated with higher CD4 recovery compared to sufficient/low inflammation status. CONCLUSIONS: In summary, baseline vitamin D deficiency was associated with diminished CD4 recovery after cART initiation; impaired CD4 recovery may contribute to the poor clinical outcomes recently observed in individuals with vitamin D deficiency. Vitamin A, selenium and sCD14 were associated with CD4 recovery but future studies are needed to further explore these relationships.

Hydroxypropyl-Beta-Cyclodextrin Reduces Inflammatory Signaling from Monocytes: Possible Implications for Suppression of HIV Chronic Immune Activation.

Monocytes from HIV-infected patients produce increased levels of inflammatory cytokines, which are associated with chronic immune activation and AIDS progression. Chronic immune activation is often not restored even in patients showing viral suppression under ART. Therefore, new therapeutic strategies to control inflammation and modulate immune activation are required. Hydroxypropyl-beta-cyclodextrin (HP-BCD) is a cholesterol-sequestering agent that has been reported to be safe for human use in numerous pharmaceutical applications and that has been shown to inactivate HIV in vitro and to control SIV infection in vivo Since cellular cholesterol content or metabolism has been related to altered cellular activation, we evaluated whether HP-BCD treatment could modulate monocyte response to inflammatory stimuli. Treatment of monocytes isolated from HIV-positive and HIV-negative donors with HP-BCD inhibited the expression of CD36 and TNF-α after LPS stimulation, independent of raft disruption. Accordingly, HP-BCD-treated cells showed significant reduction of TNF-α and IL-10 secretion, which was associated with lower mRNA expression. LPS-induced p38MAPK phosphorylation was dampened by HP-BCD treatment, indicating this pathway as a target for HP-BCD-mediated anti-inflammatory response. The expression of HLA-DR was also reduced in monocytes and dendritic cells treated with HP-BCD, which could hinder T cell activation by these cells. Our data suggest that, besides its well-known antiviral activity, HP-BCD could have an immunomodulatory effect, leading to decreased inflammatory responses mediated by antigen-presenting cells, which may impact HIV pathogenesis and AIDS progression.IMPORTANCE Chronic immune activation is a hallmark of HIV infection and is often not controlled even in patients under antiretroviral therapy. Indeed, chronic diseases with inflammatory pathogenesis are being reported as major causes of death for HIV-infected persons. Hydroxypropyl-beta cyclodextrin (HP-BCD) is a cholesterol-sequestering drug that inhibits HIV replication and infectivity in vitro and in vivo Recent studies have demonstrated the importance of cholesterol metabolism and content in different inflammatory conditions; therefore, we investigated the potential of HP-BCD as an immunomodulatory drug, regulating the activation of cells from HIV-infected patients. Treatment of monocytes with HP-BCD inhibited the expression and secretion of receptors and mediators that are usually enhanced in HIV patients. Furthermore, we investigated the molecular mechanisms associated with the immunomodulatory effect of HP-BCD. Our results indicate that, besides reducing viral replication, HP-BCD treatment may contribute to modulation of chronic immune activation associated with AIDS.

Perianesthetic and Anesthesia-Related Mortality in a Southeastern United States Population: A Longitudinal Review of a Prospectively Collected Quality Assurance Data Base.

BACKGROUND: Perianesthetic mortality (death occurring within 48 hours of an anesthetic) continues to vary widely depending on the study population examined. The authors study in a private practice physician group that covers multiple anesthetizing locations in the Southeastern United States. This group has in place a robust quality assurance (QA) database to follow all patients undergoing anesthesia. With this study, we estimate the incidence of anesthesia-related and perianesthetic mortality in this QA database. METHODS: Following institutional review board approval, data from 2011 to 2016 were obtained from the QA database of a large, community-based anesthesiology group practice. The physician practice covers 233 anesthetizing locations across 20 facilities in 2 US states. All detected cases of perianesthetic death were extracted from the database and compared to the patients' electronic medical record. These cases were further examined by a committee of 3 anesthesiologists to determine whether the death was anesthesia related (a perioperative death solely attributable to either the anesthesia provider or anesthetic technique), anesthetic contributory (a perioperative death in which anesthesia role could not be entirely excluded), or not due to anesthesia. RESULTS: A total of 785,467 anesthesia procedures were examined from the study period. A total of 592 cases of perianesthetic deaths were detected, giving an overall death rate of 75.37 in 100,000 cases (95% CI, 69.5-81.7). Mortality judged to be anesthesia related was found in 4 cases, giving a mortality rate of 0.509 in 100,000 (95% CI, 0.198-1.31). Mortality judged to be anesthesia contributory were found in 18 cases, giving a mortality of 2.29 in 100,000 patients (95% CI, 1.45-3.7). A total of 570 cases were judged to be nonanesthesia related, giving an incidence of 72.6 per 100,000 anesthetics (95% CI, 69.3-75.7). CONCLUSIONS: In a large, comprehensive database representing the full range of anesthesia practices and locations in the Southeastern United States, the rate of perianesthestic death was 0.509 in 100,000 (95% CI, 0.198-1.31). Future in-depth analysis of the epidemiology of perianesthetic deaths will be reported in later studies.

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.

Is Compliance With Surgical Care Improvement Project Cardiac (SCIP-Card-2) Measures for Perioperative ß-Blockers Associated With Reduced Incidence of Mortality and Cardiovascular-Related Critical Quality Indicators After Noncardiac Surgery?

BACKGROUND: While continuation of ß-blockers (BBs) perioperatively has become a national quality improvement measure, the relationship between BB withdrawal and mortality and cardiovascular-related critical quality indicators has not been studied in a contemporary cohort of patients undergoing noncardiac surgery. METHODS: For this retrospective study, the quality assurance database of a large community-based anesthesiology group practice was used to identify 410,288 surgical cases, 18 years of age or older, who underwent elective or emergent noncardiac surgical procedures between January 1, 2009, and December 31, 2014. Each surgical case that was withdrawn from BBs perioperatively was propensity matched by clinical and surgical characteristics to 4 cases that continued BBs perioperatively. Subsequently, multivariable conditional logistic regression analyses were performed in the matched cohort to determine the extent to which withdrawal of perioperative BBs was independently associated with mortality as the primary outcome and cardiovascular-related critical quality indicators as the secondary outcome (need for vasopressor, electrocardiographic changes requiring treatment, unplanned admission to intensive care unit, postanesthesia care unit stay >2 hours, and a combination of cardiac arrest and myocardial infarction) within 48 hours postoperatively. RESULTS: Of the 66,755 (16%) cases in the cohort admitted on BB therapy, BBs were withdrawn in 3829 (6%) and continued in 62,926 (94%). Propensity score matching resulted in an analysis cohort of 19,145 cases. Withdrawal of perioperative BBs in the multivariable conditional logistic regression analysis was significantly associated with an increased risk for mortality (odds ratio [OR], 3.61; 95% confidence interval [CI], 1.75-7.35; P = .0003), but a significantly decreased risk for need of blood pressure support requiring vasopressor initiation (OR, 0.84; 95% CI, 0.76-0.92; P = .0003) and extended postanesthesia care unit stay (OR, 0.69; 95% CI, 0.54-0.88; P = .004) within 48 hours after noncardiac surgery. CONCLUSIONS: Perioperative withdrawal of BBs was associated with increased risk for mortality within 48 hours after noncardiac surgery and with decreased risk for need of vasopressor during the early postoperative period and a shorter stay in the postanesthesia care unit.

Associations of Plasma Cytokine and Microbial Translocation Biomarkers With Immune Reconstitution Inflammatory Syndrome.

A nested case-cohort study was performed in participants of a clinical trial of first-line human immunodeficiency virus treatments to investigate plasma biomarkers of inflammation and microbial translocation for their association with immune reconstitution inflammatory syndrome (IRIS). Fifty-one of 1452 participants with baseline CD4 count <350 cells/µL developed IRIS. Plasma from 51 IRIS cases, including 6 stratified by preenrollment CD4 count ≤200 cells/µL, were analyzed and compared to 94 non-IRIS controls. At baseline, CXCL10, lipopolysaccharide, soluble CD14, 16S ribosomal DNA, and interferon-α2 were associated with greater risk of IRIS. Systemic inflammation through persistent monocyte activation and microbial translocation appear to be important in IRIS pathogenesis.

Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial.

BACKGROUND: In a placebo-controlled trial of the peptide-based therapeutic HIV-1 p24Gag vaccine candidate Vacc-4x, participants on combination antiretroviral therapy (cART) received six immunizations over 18weeks, followed by analytical treatment interruption (ATI) between weeks 28 and 52. Cell-mediated immune responses were investigated as predictors of Vacc-4x effect (VE) on viral load (VL) and CD4 count during ATI. METHODS: All analyses of week 28 responses and fold-changes relative to baseline considered per-protocol participants (Vacc-4x:placebo=72:32) resuming cART after week 40. Linear regression models with interaction tests were used. VE was estimated as the Vacc-4x-placebo difference in log10-transformed VL (VEVL) or CD4 count (VECD4). FINDINGS: A lower fold-change of CD4+ T-cell proliferation was associated with VECD4 at week 48 (p=0.036, multiplicity adjusted q=0.036) and week 52 (p=0.040, q=0.080). A higher fold-change of IFN-γ in proliferation supernatants was associated with VEVL at week 44 (p=0.047, q=0.07). A higher fold-change of TNF-α was associated with VEVL at week 44 (p=0.045, q=0.070), week 48 (p=0.028, q=0.070), and week 52 (p=0.037, q=0.074). A higher fold-change of IL-6 was associated with VEVL at week 48 (p=0.017, q=0.036). TNF-α levels (>median) were associated with VECD4 at week 48 (p=0.009, q=0.009). INTERPRETATION: These exploratory analyses highlight the potential value of investigating biomarkers in T-cell proliferation supernatants for VE in clinical studies.

Tissue Pharmacologic and Virologic Determinants of Duodenal and Rectal Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution in HIV-Infected Patients Initiating Antiretroviral Therapy.

Plasma, duodenal, and rectal tissue antiretroviral therapy (ART) drug concentrations, human immunodeficiency virus (HIV) RNA and HIV DNA copy numbers, and recovery of mucosal immunity were measured before and 9 months after initiation of 3 different ART regimens in 26 subjects. Plasma and tissue HIV RNA correlated at baseline and when 9-month declines were compared, suggesting that these compartments are tightly associated. Antiretroviral tissue:blood penetration ratios were above the 50% inhibitory concentration values in almost 100% of cases. There were no correlations between drug concentrations and HIV DNA/RNA. Importantly, no evidence was found for residual viral replication or deficient tissue drug penetration to account for delayed gastrointestinal-associated lymphoid tissue immune recovery.

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.