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Competing Interests: Conflicts of Interest: See Disclosures at the end of the article.

Background: Ataxic breathing (AB) is a well-known manifestation of opioid effects in animals and humans, but is not routinely included in monitoring for opioid-induced respiratory depression (OIRD). We quantified AB in normal volunteers receiving increasing doses of remifentanil. We used a support vector machine (SVM) learning approach with features derived from a modified Poincaré plot. We tested the hypothesis that AB may be found when bradypnea and reduced mental status are not present., Methods: Twenty-six healthy volunteers (13 female) received escalating target effect-site concentrations of remifentanil with a low baseline dose of propofol to simulate typical breathing patterns in drowsy patients who had received parenteral opioids. We derived respiratory rate (RR) from respiratory inductance plethysmography, mental alertness from the Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S), and AB severity on a 0 to 4 scale (categories ranging from none to severe) from the SVM. The primary outcome measure was sensitivity and specificity for AB to detect OIRD., Results: All respiratory measurements were obtained from unperturbed subjects during steady state in 121 assessments with complete data. The sensitivity of AB for detecting OIRD by the conventional method was 92% and specificity was 28%. As expected, 69 (72%) of the instances not diagnosed as OIRD using conventional measures were observed to have at least moderate AB., Conclusions: AB was frequently present in the absence of traditionally detected OIRD as defined by reduced mental alertness (MOAA/S score of <4) and bradypnea (RR <8 breaths/min). These results justify the need for future trials to explore replicability with other opioids and clinical utility of AB as an add-on measure in recognizing OIRD., Competing Interests: Conflicts of interest, Funding: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Anionic carboxylated cellulose nanofibers (CNF) are effective media to remove cationic contaminants from water. In this study, sustainable cationic CNF-based adsorbents capable of removing anionic contaminants were demonstrated using a simple approach. Specifically, the zero-waste nitro-oxidization process was used to produce carboxylated CNF (NOCNF), which was subsequently converted into a cationic scaffold by crosslinking with aluminum ions. The system, termed Al-CNF, is found to be effective for the removal of fluoride ions from water. Using the Langmuir isotherm model, the fluoride adsorption study indicates that Al-CNF has a maximum adsorption capacity of 43.3 mg/g, which is significantly higher than that of alumina-based adsorbents such as activated alumina (16.3 mg/g). The selectivity of fluoride adsorption in the presence of other anionic species (nitrate or sulfate) by Al-CNF at different pH values was also evaluated. The results indicate that Al-CNF can maintain a relatively high selectivity towards the adsorption of fluoride. Finally, the sequential applicability of using spent Al-CNF after the fluoride adsorption to further remove cationic contaminant such as Basic Red 2 dye was demonstrated. The low cost and relatively high adsorption capacity of Al-CNF make it suitable for practical applications in fluoride removal from water.

In this study, a sulfonation approach using chlorosulfonic acid (CSA) to prepare cellulose sulfate nanofibers (CSNFs) from raw jute fibers is demonstrated. Both elemental sulfur content and zeta potential in the CSNFs are found to increase with increasing CSA content used. However, the corresponding crystallinity in the CSNFs decreases with the increasing amount of CSA used due to degradation of cellulose chains under harsh acidic conditions. The ammonium adsorption results from the CSNFs with varying degrees of sulfonation were analyzed using the Langmuir isotherm model, and the analysis showed a very high maximum ammonium adsorption capacity (41.1 mg/g) under neutral pH, comparable to the best value from a synthetic hydrogel in the literature. The high ammonium adsorption capacity of the CSNFs was found to be maintained in a broad acidic range (pH = 2.5 to 6.5).

Background: Association between visual field test indices and The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB) is unknown. Idiopathic normal pressure hydrocephalus (iNPH) patients provide a unique set of patient data for analysis., Objective: To assess the reliability of visual field testing using the CERAD-NB in patients with iNPH and to investigate the association between visual field test results and cognitive function., Methods: 62 probable iNPH patients were subjected to comprehensive ophthalmological examination, ophthalmological optical coherence tomography imaging studies, visual field testing, and CERAD-NB. Based on visual field indices, the patients were divided into two groups: unreliable (n = 19) and reliable (n = 43). Independent T-test analysis was performed to examine the relationship between visual field test results and cognitive function. Pearson Chi-square test was used for non-continuous variables., Results: The unreliable group performed worse in CERAD-NB subtests compared to the reliable group. Statistically significant differences were observed in nine out of ten subtests, with only Clock Drawing showing no statistical significance. Pairwise comparison of the groups showed no statistical significance between amyloid-β (Aβ) biopsy, hyperphosphorylated tau biopsy, apolipoprotein E allele or the ophthalmological status of the patient. But there was a statistically significant difference in cerebrospinal fluid Aβ42 and age between the groups., Conclusions: Patients with unreliable visual field tests performed worse on CERAD-NB subtests. CERAD-NB subtests do not provide a specific cut-off value to refrain patients from visual field testing. Should patients with unreliable visual field tests be screened for cognitive impairment?

Purpose of Review: This review describes recent prospective and retrospective work exploring the incidence and clinical consequence of sugammadex-induced bradycardia and an update of recent evidence and adverse event reports to the United States Food and Drug Administration regarding the incidence of sugammadex induced bradycardia., Recent Findings: This work suggests that the incidence of sugammadex-induced bradycardia can range from 1 to 7% depending on the definition to reverse moderate to deep neuromuscular blockade. For most instances, the bradycardia is inconsequential. For those instances that have hemodynamic instability, the adverse physiology is easily treated with appropriate vasoactive agents. One study demonstrated that the incidence of bradycardia from sugammadex is less than with neostigmine. There are several case reports that describe marked bradycardia with cardiac arrest from reversal with sugammadex. The incidence of this type of reaction to sugammadex appears to be very rare. Data from the United States Food and Drug Administration's Adverse Event Reporting System public dashboard corroborates this presence of this rare finding., Summary: Sugammadex-induced bradycardia is common and, in most instances, of minimal clinical consequence. Nevertheless, anesthesia providers should maintain proper monitoring and vigilance to treat hemodynamical instability with each administration of sugammadex., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although physical activity (PA) has been recognized as a favourable factor in the prevention of various diseases, including certain forms of cancer, the relationship between PA and gastric cancer (GC) is not yet fully understood. This study aims to provide data from a pooled analysis of case-control studies within the Stomach cancer Pooling (StoP) Project to estimate the association between leisure-time PA and the occurrence of GC., Methods: Six case-control studies from StoP project collected data on leisure-time PA, for a total of 2,343 cases and 8,614 controls. Subjects were classified into three leisure-time PA categories, either none/low, intermediate or high, based on study-specific tertiles. We used a two-stage approach. Firstly, we applied multivariable logistic regression models to obtain study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) then, we used a random-effect models to obtain pooled effect estimates. We performed stratified analyses according to demographic, lifestyle and clinical covariates., Results: The meta-analysis showed ORs of GC with no significant differences between intermediate vs low and high vs low PA level (OR 1.05 [95%CI 0.76-1.45]; OR 1.23 [95%CI 0.78-1.94], respectively). GC risk estimates did not strongly differ across strata of selected covariates except for age ≤ 55 years old (high vs low level: OR 0.72 [95%CI 0.55-0.94]) and for control population-based studies (high vs low level: OR 0.79 [95%CI 0.68-0.93])., Conclusions: No association was found between leisure time PA and GC, apart from a slight suggestion of decreased risk below age 55 and in control population-based studies. These results may reflect specific characteristics of GC at a younger age, or the presence of a cohort effect mediating and interacting with socioeconomic determinants of GC The different distribution of PA levels among hospitalized controls could have led to an underestimated effect of PA on GC risk., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mariani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Taxanes, particularly paclitaxel and docetaxel, are chemotherapeutic agents commonly used to treat breast cancers. A frequent side effect is chemotherapy-induced peripheral neuropathy (CIPN) that occurs in up to 70% of all treated patients and impacts the quality of life during and after treatment. CIPN presents as glove and stocking sensory deficits and diminished motor and autonomic function. Nerves with longer axons are at higher risk of developing CIPN. The causes of CIPN are multifactorial and poorly understood, limiting treatment options. Pathophysiologic mechanisms can include: (i) disruptions of mitochondrial and intracellular microtubule functions, (ii) disruption of axon morphology, and (iii) activation of microglial and other immune cell responses, among others. Recent work has explored the contribution of genetic variation and selected epigenetic changes in response to taxanes for any insights into their relation to pathophysiologic mechanisms of CIPN20, with the hope of identifying predictive and targetable biomarkers. Although promising, many genetic studies of CIPN are inconsistent making it difficult to develop reliable biomarkers of CIPN. The aims of this narrative review are to benchmark available evidence and identify gap s in the understanding of the role genetic variation has in influencing paclitaxel's pharmacokinetics and cellular membrane transport potentially related to the development of CIPN., Competing Interests: DMR has received research funding from Novo Nordisk, has an equity stake in Clarified Precision Medicine, and has intellectual property related to treatment decision making in the context of type 2 diabetes and liver cancer. No other potential conflicts of interest relevant to this article were reported. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Johnson, Sharma, Henry, Wei, Bie, Hershberger, Rhoades, Sen, Johnson, Steenblik, Hockings, Budd, Eng, Foss and Rotroff.)

Background: There is insufficient prospective evidence regarding the relationship between surgical experience and prolonged opioid use and pain. The authors investigated the association of patient characteristics, surgical procedure, and perioperative anesthetic course with postoperative opioid consumption and pain 3 months postsurgery. The authors hypothesized that patient characteristics and intraoperative factors predict opioid consumption and pain 3 months postsurgery., Methods: Eleven U.S. and one European institution enrolled patients scheduled for spine, open thoracic, knee, hip, or abdominal surgery, or mastectomy, in this multicenter, prospective observational study. Preoperative and postoperative data were collected using patient surveys and electronic medical records. Intraoperative data were collected from the Multicenter Perioperative Outcomes Group database. The association between postoperative opioid consumption and surgical site pain at 3 months, elicited from a telephone survey conducted at 3 months postoperatively, and demographics, psychosocial scores, pain scores, pain management, and case characteristics, was analyzed., Results: Between September and October 2017, 3,505 surgical procedures met inclusion criteria. A total of 1,093 cases were included; 413 patients were lost to follow-up, leaving 680 (64%) for outcome analysis. Preoperatively, 135 (20%) patients were taking opioids. Three months postsurgery, 96 (14%) patients were taking opioids, including 23 patients (4%) who had not taken opioids preoperatively. A total of 177 patients (27%) reported surgical site pain, including 45 (13%) patients who had not reported pain preoperatively. The adjusted odds ratio for 3-month opioid use was 18.6 (credible interval, 10.3 to 34.5) for patients who had taken opioids preoperatively. The adjusted odds ratio for 3-month surgical site pain was 2.58 (1.45 to 4.4), 4.1 (1.73 to 8.9), and 2.75 (1.39 to 5.0) for patients who had site pain preoperatively, knee replacement, or spine surgery, respectively., Conclusions: Preoperative opioid use was the strongest predictor of opioid use 3 months postsurgery. None of the other variables showed clinically significant association with opioid use at 3 months after surgery., (Copyright © 2023, the American Society of Anesthesiologists. All Rights Reserved.)

Abstract: Technology-enhanced rehabilitation can improve access to training activities in multiple care delivery settings and may improve patient outcomes. However, the rate at which rehabilitation technology is being developed makes it difficult for healthcare systems to keep pace with the volume of products emerging in this space. Formal processes are needed to help healthcare systems review products as they emerge and to determine whether they should be incorporated into clinical practice. Here, we describe an approach to reviewing emerging rehabilitation technologies as performed by the Center for Emerging Rehabilitation Technology at our institution. Developed using an iterative approach, the rehabilitation technology review process used by the Center for Emerging Rehabilitation Technology team classifies technologies into the following three categories: (1) for clinical deployment, (2) for innovation in product development/product-market fit testing, and (3) for research, for example, a sponsored clinical trial. We describe the processes used to evaluate, categorize, investigate, and integrate rehabilitation technology, share our experience with the review process, and make recommendations for other institutions who may wish to implement rehabilitation technology into clinical practice., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Ultrafiltration (UF) is a common technique used in wastewater treatments. However, the issue of membrane fouling in UF can greatly hinder the effectiveness of the treatments. This study demonstrated a low-fouling composite cellulose membrane system based on microfibrillated cellulose (MFC) and silica nanoparticle additives. The incorporation of 'non-spherical' silica nanoparticles was found to exhibit better structural integration in the membrane (i.e., minimal aggregation of silica nanoparticles in the membrane scaffold) as compared to spherical silica. The resulting composite membranes were tested for UF using local wastewater, where the best-performing membrane exhibited higher permeation flux than commercial polyvinylidene difluoride (PVDF) and polyether sulfone (PES) membranes while maintaining a high separation efficiency (~99.6%) and good flux recovery ratio (>90%). The analysis of the fouling behavior using different models suggested that the processes of cake layer formation and pore-constriction were probably two dominant fouling mechanisms, likely due to the presence of humic substances in wastewater. The demonstrated cellulose composite membrane system showed low-fouling and high restoration capability by a simple hydraulic cleaning method due to the super hydrophilic nature of the cellulose scaffold containing silica nanoparticles.

In this Pro-Con article, we debate the merits of using quantitative neuromuscular blockade monitoring. Consensus guidelines recommend their use to guide the administration of nondepolarizing neuromuscular blockade and reversal agents. A major impediment to this guideline is that until recently, reliable quantitative neuromuscular blockade monitors have not been widely available. Without them, anesthesia providers have been trained with and are adept at using a variety of qualitative neuromuscular blockade monitors otherwise known as peripheral nerve stimulators. Although perhaps less accurate, anesthesia providers find them reliable and easy to use. They have a long track record of using them with the perception that their use leads to effective neuromuscular blockade reversal and minimizes clinically significant adverse events from residual neuromuscular blockade. In the recent past, 2 disruptive developments have called upon anesthesia care providers to reconsider their practice in neuromuscular blockade administration, reversal, and monitoring. These include: (1) commercialization of more reliable quantitative neuromuscular monitors and (2) widespread use of sugammadex, a versatile reversal agent of neuromuscular blockade. Sugammadex appears to be so effective at rapidly and effectively reversing even the deepest of neuromuscular blockades, and it has left anesthesia providers wondering whether quantitative monitoring is indeed necessary or whether conventional, familiar, and less expensive qualitative monitoring will suffice? This Pro-Con debate will contrast anesthesia provider perceptions with evidence surrounding the use of quantitative neuromuscular blockade monitors to explore whether quantitative neuromuscular monitoring (NMM) is just another technology solution looking for a problem or a significant advance in NMM that will improve patient safety and outcomes., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2022 International Anesthesia Research Society.)

Objective: This study aimed to evaluate and quantify the relationship between coffee and gastric cancer using a uniquely large dataset from an international consortium of observational studies on gastric cancer, including data from 18 studies, for a total of 8198 cases and 21 419 controls., Methods: A two-stage approach was used to obtain the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for coffee drinkers versus never or rare drinkers. A one-stage logistic mixed-effects model with a random intercept for each study was used to estimate the dose-response relationship. Estimates were adjusted for sex, age and the main recognized risk factors for gastric cancer., Results: Compared to never or rare coffee drinkers, the estimated pooled OR for coffee drinkers was 1.03 (95% CI, 0.94-1.13). When the amount of coffee intake was considered, the pooled ORs were 0.91 (95% CI, 0.81-1.03) for drinkers of 1-2 cups per day, 0.95 (95% CI, 0.82-1.10) for 3-4 cups, and 0.95 (95% CI, 0.79-1.15) for five or more cups. An OR of 1.20 (95% CI, 0.91-1.58) was found for heavy coffee drinkers (seven or more cups of caffeinated coffee per day). A positive association emerged for high coffee intake (five or more cups per day) for gastric cardia cancer only., Conclusions: These findings better quantify the previously available evidence of the absence of a relevant association between coffee consumption and gastric cancer., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Taxanes are a class of chemotherapeutics commonly used to treat various solid tumors, including breast and ovarian cancers. Taxane-induced peripheral neuropathy (TIPN) occurs in up to 70% of patients, impacting quality of life both during and after treatment. TIPN typically manifests as tingling and numbness in the hands and feet and can cause irreversible loss of function of peripheral nerves. TIPN can be dose-limiting, potentially impacting clinical outcomes. The mechanisms underlying TIPN are poorly understood. As such, there are limited treatment options and no tools to provide early detection of those who will develop TIPN. Although some patients may have a genetic predisposition, genetic biomarkers have been inconsistent in predicting chemotherapy-induced peripheral neuropathy (CIPN). Moreover, other molecular markers (eg, metabolites, mRNA, miRNA, proteins) may be informative for predicting CIPN, but remain largely unexplored. We anticipate that combinations of multiple biomarkers will be required to consistently predict those who will develop TIPN. Methods: To address this clinical gap of identifying patients at risk of TIPN, we initiated the Genetics and Inflammatory Markers for CIPN (GENIE) study. This longitudinal multicenter observational study uses a novel, multimodal approach to evaluate genomic variation, metabolites, DNA methylation, gene expression, and circulating cytokines/chemokines prior to, during, and after taxane treatment in 400 patients with breast cancer. Molecular and patient reported data will be collected prior to, during, and after taxane therapy. Multi-modal data will be used to develop a set of comprehensive predictive biomarker signatures of TIPN. Conclusion: The goal of this study is to enable early detection of patients at risk of developing TIPN, provide a tool to modify taxane treatment to minimize morbidity from TIPN, and improved patient quality of life. Here we provide a brief review of the current state of research into CIPN and TIPN and introduce the GENIE study design.

The evidence supporting the intraoperative use of processed electroencephalography (pEEG) monitoring to guide anesthetic delivery is growing rapidly. This article reviews the key features of electroencephalography (EEG) waveforms and their clinical implications in select patient populations and anesthetic techniques. The first patient topic reviewed is the vulnerable brain. This term has emerged as a description of patients who may exhibit increased sensitivity to anesthetics and/or may develop adverse neurocognitive effects following anesthesia. pEEG monitoring of patients who are known to have or are suspected of having vulnerable brains, with focused attention on the suppression ratio, alpha band power, and pEEG indices, may prove useful. Second, pEEG monitoring along with vigilant attention to anesthetic delivery may minimize the risk of intraoperative awareness when administering a total intravenous anesthesia in combination with a neuromuscular blockade. Third, we suggest that processed EEG monitoring may play a role in anesthetic and resuscitative management when adverse changes in blood pressure occur. Fourth, pEEG monitoring can be used to better identify anesthesia requirements and guide anesthetic titration in patients with known or suspected substance use.

In this study, granulated activated charcoal (GAC) and bio charcoal (BC) is used as a filler in P3 biosand bag filter to study their filtration performance against a range of fluoride impurities from 1-1400 mg/L. A set of experiments are done to analyze the filtration efficiency of the sandbag filter against fluoride impurities after incorporating different amounts (e.g., 0.2, 2 kg) and a combination of GAC and BC. A combination of filler GAC and BC (1 kg each) have exhibited excellent results with 100% fluoride removal efficiency against 5 mg/L fluoride impurities for an entire experimental time of 165 min. It is because of the synergetic effect of adsorption caused by the high surface area (739 m 2 /g) of GAC and hydroxyapatite groups in BC. The data from remediation experiments using individual GAC and BC are fitted into the Langmuir and Freundlich Isotherm Models to check their adsorption mechanism and determine GAC and BC's maximum adsorption capacity ( Q m ). The remediation data for both GAC and BC have shown the better fitting to the Langmuir Isotherm Model with a high R 2 value of 0.994 and 0.970, respectively, showing the excellent conformity with monolayer adsorption. While the GAC and BC have presented negative Kf values of -1.08 and -0.72, respectively, for Freundlich Model, showing the non-conformity to multilayer adsorption. The Q m values obtained from Langmuir Model for GAC is 6.23 mg/g, and for BC, it is 9.13 mg/g. The pH study on adsorption efficiency of individual GAC and BC against 5 mg/L of fluoride impurities indicates the decrease in removal efficiency with an increase in pH from 3 to 9. For example, BC has shown removal efficiency of 99.8% at pH 3 and 99.5% at pH 9, while GAC has exhibited removal efficiency of 96.1% at pH 3 and 95.9% at pH 9. Importantly, this study presents the significance of the synergetic application of GAC and BC in the filters, where GAC and BC are different in their origin, functionalities, and surface characteristics.

Introduction: The retina and brain exhibit similar pathologies in patients diagnosed with neurodegenerative diseases. The ability to access the retina through imaging techniques opens the possibility for non-invasive evaluation of Alzheimer's disease (AD) pathology. While retinal amyloid deposits are detected in individuals clinically diagnosed with AD, studies including preclinical individuals are lacking, limiting assessment of the feasibility of retinal imaging as a biomarker for early-stage AD risk detection., Methods: In this small cross-sectional study we compare retinal and cerebral amyloid in clinically normal individuals who screened positive for high amyloid levels through positron emission tomography (PET) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial as well as a companion cohort of individuals who exhibited low levels of amyloid PET in the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study. We quantified the number of curcumin-positive fluorescent retinal spots from a small subset of participants from both studies to determine retinal amyloid deposition at baseline., Results: The four participants from the A4 trial showed a greater number of retinal spots compared to the four participants from the LEARN study. We observed a positive correlation between retinal spots and brain amyloid, as measured by the standardized uptake value ratio (SUVr)., Discussion: The results of this small pilot study support the use of retinal fundus imaging for detecting amyloid deposition that is correlated with brain amyloid PET SUVr. A larger sample size will be necessary to fully ascertain the relationship between amyloid PET and retinal amyloid both cross-sectionally and longitudinally., Competing Interests: Ken Johnson is an employee at NeuroVision Imaging Inc., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

We have developed a real-time graphical display that presents anesthetic pharmacology data (drug effect site concentrations (Ce) and probability of anesthetic effects including hypnosis, loss of response to tracheal intubation), improving a previous prototype. We hypothesized that the use of the display alters (1) clinical behavior of anesthesiologists (i.e., Ce of isoflurane and fentanyl at the end of anesthesia), (2) fentanyl dose during the first 30 min of recovery in the post anesthesia care unit (PACU), and that the response of clinicians to the display in terms of workload and utility is favorable. The display was evaluated in a two-group, non-randomized prospective observational study of 30 patients undergoing general anesthesia using isoflurane and fentanyl. The isoflurane-predicted Ce was lower in the display group (without-display: 0.64% ± 0.06%; with-display: 0.42 ± 0.04%; t 23.9  = 3.17, P = 0.004 < adjusted alpha 0.05/2). The difference in fentanyl-predicted Ce did not achieve statistical significance (without-display: 1.5 ± 0.1 ng/ml; with-display: 2.0 ± 0.2 ng/ml; t 25.5  = 2.26, P = 0.03 > adjusted alpha 0.05/2) (means ± standard error). A joint test of isoflurane and fentanyl Ce with respect to the display condition rejected the null hypothesis of no differences (Hotelling T2, P = 0.01), supporting our primary hypothesis. The total fentanyl per patient during the first 30 min in the PACU with the display was 75.0 ± 62.7 µg and that without the display was 83.0 ± 74.7 µg. There was no significant difference between the groups (means ± standard deviation, P = 0.75). There were no differences in perceived workload. Use of the display does not appear to be cognitively burdensome and may change the anesthesiologist's dosing regimen.

Audiovisual distraction (AVD) has been used to augment or replace procedural sedation. We investigated whether AVD in patients having total hip (THA) or total knee arthroplasty (TKA) under spinal anesthesia would reduce self-administered propofol consumption during surgery. 50 participants were randomized equally into a patient-controlled sedation (PCS) group or AVD group. All participants were given a spinal block and a propofol PCS device prior to surgery. In addition, Group AVD participants selected and watched a movie or documentary film on a tablet device with noise-cancelling headphones during surgery. The primary outcome of this study was total propofol consumption standardized as mcg/kg/min. Secondary outcomes evaluated increased supplemental oxygen use, rescue airway interventions, hypotension, disruptive movement events during surgery, sedation, and satisfaction with anesthesia scores. Historical clinician-controlled propofol usage at our institution over the previous 2 years were recorded. There was no significant difference in median propofol consumption between Groups PCS and AVD, 8.4 mcg/kg/min (1.6-18.9) vs 4 mcg/kg/min (0-9) (P = 0.29), respectively. Historical clinician-controlled usage of propofol demonstrated a median of 39.3 mcg/kg/min (29.2-51.2). There were few differences in the secondary outcome measures. The use of AVD did not reduce patient-controlled propofol consumption in patients having a THA or TKA surgery under spinal anesthesia.

Opioids may influence inflammation. We compared genes associated with pain and inflammation in patients who consumed opioids (3-120 mg of oral morphine equivalents per day) with those who did not for differential expression. White blood cells were assayed in 20 patients presenting for total lower extremity joint replacement. We focused on messenger ribonucleic acid expression of complement proteins. We report that the expression of a complement inhibitor, complement 4 binding protein A, was reduced, and the expression of a complement activator, complement factor D, was increased in opioid-consuming patients. We conclude that opioid consumption may influence expression of complement activators and inhibitors., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 International Anesthesia Research Society.)

The aim of this study was to test the effects of CPAP on moderately sedated patients undergoing colonoscopy. Our hypothesis was that CPAP can reduce the incidence and duration of obstructive apnea and hemoglobin oxygen desaturation in patients undergoing procedural sedation for colonoscopy. Two groups of consenting adult patients scheduled to undergo routine colonoscopy procedures and sedated with propofol and fentanyl were monitored in this study: control and intervention. Patients in the intervention group were connected via a facemask to a ventilator that delivered supplemental oxygen (100%) through a standard air-cushion mask. The mask had a built-in leak to facilitate CO 2 clearance during CPAP. Patients in the control group received 2-10 L/min of oxygen via nasal cannula or non-rebreather mask. Subjects in the control group were collected in a prior study and used as historical controls. The primary outcome measures were the number of apneic events and the cumulative duration of apneic events. An apneic event was defined as a period longer than 10 s without respiration. The secondary outcome was the area under the curve (AUC) for the arterial oxygen saturation less than 90% versus time during sedative and analgesic administration (time (s) below threshold multiplied by percent below threshold). A desaturation event was defined as a period of time during which arterial oxygen saturation was less than 90%. 29 patients were enrolled in the intervention group and 156 patients were previously enrolled in the control group as part of an earlier study. The median number of apneic events in the control group was 7 compared to 0 in the intervention group. The intervention group experienced apnea less than 1% of the total procedure time compared to 17% in the control group (p < 0.001). There were no desaturation events observed in the 29 patients in the intervention group. In contrast, 27 out of 156 patients in the control group experienced a desaturation event. Average AUC of patients in the control group was 70%-s (time (s) * oxygen saturation below < 90%) (95% CI 32.34-108.60%) whereas the average AUC in intervention group patients was 0%-s (% time (s) * oxygen saturation < 90%) (95% CI 0-0%), p = 0.01. This preliminary study found that CPAP via a tight-fitting mask may be an effective tool to reduce the incidence and duration of obstructive apneic events as well as hemoglobin oxygen desaturation during lower endoscopy procedures that use propofol and fentanyl for sedation.Clinical Trial Registration ClinicalTrials.gov ID: NCT02623270. https://clinicaltrials.gov/ct2/show/NCT02623270 .

Research aim: To model the annual value of a novel ready-to-use, room-temperature stable liquid glucagon rescue pen and prefilled syringe (GRP, G-PFS; Xeris Pharmaceuticals, Inc.) for treatment of severe hypoglycemia events (SHE) versus current lyophilized powder glucagon emergency kits (GEK). GRP is a prefilled auto-injector designed to promptly administer concentrated liquid glucagon in a simple two-step process. G-PFS is a stable liquid formulation of glucagon in a prefilled syringe. In simulated emergencies, GRP and G-PFS demonstrated high functional efficacy, where 99% of users successfully administered a full-dose of drug. Studies with currently available injectable GEK suggest very low success rates (6-31%). The high functional efficacy of GRP and G-PFS significantly reduces user errors and may reduce utilization across emergency medical services (EMS), emergency departments (ED), and inpatient and outpatient costs for SHE. Methods: To estimate the economic impact of GRP and G-PFS, we developed a one-year budget impact model from a US commercial health plan perspective. Cost offsets from successful glucagon administration incorporated EMS, ED, inpatient, and outpatient utilization. Diabetes prevalence and event probabilities were estimated from publicly-available sources and clinical expert opinion. Costs (US$) were obtained from the 2018 Medicare Fee Schedules and adjusted to represent commercial payer costs. Results: GRP and G-PFS led to fewer EMS, ED, inpatient, and outpatient costs compared to GEK and no kit, resulting in total per-patient SHE costs of $2,564, $3,606, and $3,849, respectively. Costs for 1 million covered lives were 8.2 million following the introduction of GRP and G-PFS compared to almost 9 million before GRP and G-PFS. Limitations: The model is limited by reliance on assumptions based on expert opinion for key variables, primarily the probability of: (1) ambulance calls, (2) ambulance transport to the ED, and (3) non-ambulance transport to the ED. Conclusions: A budget impact model suggests GRP and G-PFS can lead to significant annual cost savings for US commercial payers.

Long-distance running has become increasingly popular during the past decades. Many running patients pose questions to their orthopaedic surgeons regarding risks, benefits, and running techniques. This article identifies 11 running-related questions that patients may ask and provides information to help answer those questions. This review discusses data on the health benefits of running, common running injuries, the relationship between running and osteoarthritis, recommendations regarding running after orthopaedic surgery, running shoes, and other questions that may arise when treating the running athlete.

Background: Opioid-induced respiratory depression (OIRD) is traditionally recognized by assessment of respiratory rate, arterial oxygen saturation, end-tidal CO2, and mental status. Although an irregular or ataxic breathing pattern is widely recognized as a manifestation of opioid effects, there is no standardized method for assessing ataxic breathing severity. The purpose of this study was to explore using a machine-learning algorithm for quantifying the severity of opioid-induced ataxic breathing. We hypothesized that domain experts would have high interrater agreement with each other and that a machine-learning algorithm would have high interrater agreement with the domain experts for ataxic breathing severity assessment., Methods: We administered target-controlled infusions of propofol and remifentanil to 26 healthy volunteers to simulate light sleep and OIRD. Respiration data were collected from respiratory inductance plethysmography (RIP) bands and an intranasal pressure transducer. Three domain experts quantified the severity of ataxic breathing in accordance with a visual scoring template. The Krippendorff alpha, which reports the extent of interrater agreement among N raters, was used to assess agreement among the 3 domain experts. A multiclass support vector machine (SVM) was trained on a subset of the domain expert-labeled data and then used to quantify ataxic breathing severity on the remaining data. The Vanbelle kappa was used to assess the interrater agreement of the machine-learning algorithm with the grouped domain experts. The Vanbelle kappa expands on the Krippendorff alpha by isolating a single rater-in this case, the machine-learning algorithm-and comparing it to a group of raters. Acceptance criteria for both statistical measures were set at >0.8. The SVM was trained and tested using 2 sensor inputs for the breath marks: RIP and intranasal pressure., Results: Krippendorff alpha was 0.93 (95% confidence interval [CI], 0.91-0.95) for the 3 domain experts. Vanbelle kappa was 0.98 (95% CI, 0.96-0.99) for the RIP SVM and 0.96 (0.92-0.98) for the intranasal pressure SVM compared to the domain experts., Conclusions: We concluded it may be feasible for a machine-learning algorithm to quantify ataxic breathing severity in a manner consistent with a panel of domain experts. This methodology may be helpful in conjunction with traditional measures to identify patients experiencing OIRD.

The need to reduce the dose of intravenous anesthetic in the setting of hemorrhagic shock is a well-established clinical dogma. Considered collectively,; the body of information concerning the behavior of intravenous anesthetics during hemorrhagic shock, drawn from animal and human data, confirms that clinical dogma and informs the rational selection and administration of intravenous anesthetics in the setting of hemorrhagic shock. The physiologic changes during hemorrhagic shock can alter pharmacokinetics and pharmacodynamics of intravenous anesthetics. Decreased size of the central compartment and central clearance caused by shock physiology lead to an altered dose-concentration relationship. For most agents and adjuncts, shock leads to substantially higher concentrations and increased effect. The notable exception is etomidate, which has relatively unchanged pharmacokinetics during shock. Increased concentrations lead to increased primary effect as well as increased side effects, notably cardiovascular effects. Pharmacokinetic changes are essentially reversed for all agents by fluid resuscitation. Propofol is unique among agents in that, in addition to the pharmacokinetic changes, it exhibits increased potency during shock. The pharmacodynamic changes of propofol persist despite fluid resuscitation. The persistence of these pharmacodynamic changes during shock is unlikely to be due to increased endogenous opiates, but is most likely due to increased fraction of unbound propofol. The stage of shock also appears to influence the pharmacologic changes. The changes are more rapid and pronounced as shock physiology progresses to the uncompensated stage. Although scant, human data corroborate the findings of animal studies. Both the animal and human data inform the rational selection and administration of intravenous anesthetics in the setting of hemorrhagic shock. The well-entrenched clinical dogma that etomidate is a preferred induction agent in patients experiencing hemorrhagic shock is firmly supported by the evidence. Propofol is a poor choice for induction or maintenance of anesthesia in severely bleeding patients, even with resuscitation; this can include emergent trauma cases or scheduled cases that routinely have mild or moderate blood loss.

Synthetic rubber produced from nonrenewable fossil fuel requires high energy costs and is dependent on the presumed unstable petroleum price. Natural rubber latex (NRL) is one of the major alternative sustainable rubber sources since it is derived from the plant ' Hevea brasiliensis '. Our study focuses on integrating sustainably processed carboxycellulose nanofibers from untreated jute biomass into NRL to enhance the mechanical strength of the material for various applications. The carboxycellulose nanofibers (NOCNF) having carboxyl content of 0.94 mmol/g was prepared and integrated into its nonionic form (-COONa) for its higher dispersion in water to increase the interfacial interaction between NRL and NOCNF. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) analyses of NOCNF showed the average dimensions of nanofibers were length (L) = 524 ± 203 nm, diameter (D) 7 ± 2 nm and thickness 2.9 nm. Furthermore, fourier transform infra-red spectrometry (FTIR) analysis of NOCNF depicted the presence of carboxyl group. However, the dynamic light scattering (DLS) measurement of NRL demonstrated an effective diameter in the range of 643 nm with polydispersity of 0.005. Tensile mechanical strengths were tested to observe the enhancement effects at various concentrations of NOCNF in the NRL. Mechanical properties of NRL/NOCNF films were determined by tensile testing, where the results showed an increasing trend of enhancement. With the increasing NOCNF concentration, the film modulus was found to increase quite substantially, but the elongation-to-break ratio decreased drastically. The presence of NOCNF changed the NRL film from elastic to brittle. However, at the NOCNF overlap concentration (0.2 wt. %), the film modulus seemed to be the highest.

Gene variants may contribute to individual differences in the experience of pain and the efficacy and reward of treatments. We explored gene variation in opioid-naïve and opioid-consuming patients undergoing elective lower extremity total joint replacement. We focused on 3 gene pathways including prostaglandin, gamma-aminobutyric acid (GABA)-ergic reward, and hepatic metabolism pathways. We report that for genes with possible or probable deleterious impact in these 3 pathways, opioid consumers had more gene variants than opioid-naïve patients (median 3 vs 1, P = .0092). We conclude that chronic opiate users may have genetic susceptibility to altered responses in reward/dependency and pain/inflammation pathways.

Objective: To assess whether intravenous immunoglobulin (IVIG) in subjects with mild cognitive impairment (MCI) results in a reduction in amyloid in the central nervous system (CNS)., Methods: Five subjects with MCI underwent baseline Florbetapir positron emission tomography and retinal autofluorescent imaging. All were administered IVIG (Octagam 10%) at 0.4 g/kg every 14 days for a total of 5 infusions. After 3 months, standard uptake value ratio (SUVR) and amyloid retinal deposits were reassessed., Results: Three subjects had a reduction in amyloid SUVR and all 5 subjects had a reduction in amyloid retinal deposits in at least 1 eye., Conclusions: A short course of IVIG over 2 months removes a measurable amount of amyloid from the CNS in persons with MCI.

Arsenite (As(III)) contamination in drinking water has become a worldwide problem in recent years, which leads to development of various As(III) remediation approaches. In this study, two biomass-based nanostructured materials, microscale dialdehyde cellulose-cysteine (MDAC-cys) and nanoscale dialdehyde cellulose-cysteine (NDAC-cys) fibers, have been prepared from wood pulp. Their As(III) removal efficiencies and mechanism were determined by combined adsorption, atomic fluorescence spectrometry, microscopy (scanning electron microscopy, transmission electron microscopy, and atomic force microscopy), and spectroscopy (Fourier transform infrared, 13 C CPMAS NMR) methods. The adsorption results of these materials could be well described by the Freundlich isotherm model, where the maximum adsorption capacities estimated by the Langmuir isotherm model were 344.82 mg/g for MDAC-cys and 357.14 mg/g for NDAC-cys, respectively. Both MDAC-cys and NDAC-cys materials were further characterized by X-ray diffraction and thermogravimetric analysis, where the results indicated that the thiol groups (the S content in MDAC-cys was 12.70 and NDAC-cys was 17.15%) on cysteine were primarily responsible for the adsorption process. The nanostructured MDAC-cys system appeared to be more suitable for practical applications because of its high cost-effectiveness., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Titrating an intraoperative anesthetic to achieve the postoperative goals of rapid emergence and prolonged analgesia can be difficult because of inter-patient variability and the need to provide intraoperative sedation and analgesia. Modeling pharmacokinetics and pharmacodynamics of anesthetic administrations estimates drug concentrations and predicted responses to stimuli during anesthesia. With utility of these PK/PD models we created an algorithm to optimize the intraoperative dosing regimen. We hypothesized the optimization algorithm would find a dosing regimen that would increase the postoperative duration of analgesia, not increase the time to emergence, and meet the intraoperative requirements of sedation and analgesia. To evaluate these hypotheses we performed a simulation study on previously collected anesthesia data. We developed an algorithm to recommend different intraoperative dosing regimens for improved post-operative results. To test the post-operative results of the algorithm we tested it on previously collected anesthesia data. An anesthetic dataset of 21 patients was obtained from a previous study from an anesthetic database at the University of Utah. Using the anesthetic records from these surgeries we modeled 21 patients using the same patient demographics and anesthetic requirements as the dataset. The anesthetic was simulated for each of the 21 patients with three different dosing regimens. The three dosing regimens are: from the anesthesiologist as recorded in the dataset (control group), from the algorithm in the clinical scenario one (test group), and from the algorithm in the clinical scenario two (test group). We created two clinical scenarios for the optimization algorithm to perform; one with normal general anesthesia constraints and goals, and a second condition where a delayed time to emergence is allowed to further maximize the duration of analgesia. The algorithm was evaluated by comparing the post-operative results of the control group to each of the test groups. Comparing results between the clinical scenario 1 dosing to the actual dosing showed a median increase in the duration of analgesia by 6 min and the time to emergence by 0.3 min. This was achieved by decreasing the intraoperative remifentanil infusion rate, increased the fentanyl dosing regimen, and not changing the propofol infusion rate. Comparing results between the clinical scenario 2 dosing to the actual dosing showed a median increase in the duration of analgesia by 26 min and emergence by 1.5 min. To dosing regimen from clinical scenario 2 greatly increased the fentanyl dosing regimen and greatly decreased the remifentanil infusion rate with no change to the propofol infusion rate. The results from this preliminary analysis of the optimization algorithm appear to imply that it can operate as intended. However a clinical study is warranted to determine to what extent the optimization algorithm determined optimal dosing regimens can maximize the postoperative duration of analgesia without delaying the time to emergence in a clinical setting.

We implemented a pharmacokinetic/pharmacodynamic (PK/PD) based optimization algorithm recommending intraoperative Remifentanil and Propofol infusion rates to minimize time to emergence and maximize the duration of analgesia in a clinical setting. This feasibility study tested the clinical acceptance of the optimization algorithm's recommendations during scoliosis surgical repair for 14 patients. Anesthesiologist accepted 359/394 (91%) of the recommendations given on the basis of the optimization algorithm. While following the optimization's recommendations the anesthesiologist decreased Propofol infusions from an average of 164-135 mcg/kg/min [p = 0.002] and increased Remifentanil infusions from an average of 0.22-0.30 mcg/kg/min [p = 0.004]. The anesthesiologists appeared to accept and follow the recommendations from a PK/PD based optimization algorithm.

Purpose of Review: This review summarizes key features of adverse airway and respiratory events for which sedation providers must be prepared to diagnose and treat in a timely manner. Key features include elements of the presedation patient evaluation that predict adverse airway and respiratory events; patient profiles, target sedation levels, and procedure types that should prompt a consult with an anesthesiologist; necessary clinical skills, essential equipment, and reversal drugs necessary to manage adverse airway and respiratory events; and a proposed airway rescue pathway that describes a sequence of interventions and prompts to call for help when encountering an adverse airway or respiratory event., Recent Findings: Several studies have reported adverse events from sedation. Although the overall rate can approach 4.5%, the incidence of events associated with severe harm is low (e.g., <0.5%). Some that are most harmful are prolonged ventilatory compromise leading to hypoxic brain injury or death. Inadequate clinical skills that contribute to these poor outcomes include undetected or delayed detection of hypopnea, apnea, and partial or complete airway obstruction, inadequate rescue skills to manage drug-induced ventilatory depression or airway obstruction, and/or a delay or no attempt to call for expert help followed by a timely response and intervention from that expert help., Summary: To improve outcomes in detecting and managing adverse airway and respiratory events, nonanesthesiologists sedation practitioners must be trained in patient selection, monitoring, pharmacology, physiology, and airway management. One gap in sedation training curriculum is a roadmap to use when managing an adverse airway or respiratory events. This review puts forth a suggested airway rescue pathway for nonanesthesiologist sedation practitioners to use as a decision aid during an adverse airway or respiratory event associated with procedural sedation.

Background: Numerous technologies are used to monitor respiratory rates in nonintubated patients. No technology has emerged as the standard. The primary aim of this study was to assess the limits of agreement between a reference sensor signal (respiratory inductance plethysmography bands) and 7 alternative sensor signals (nasal capnometer, nasal pressure transducer, oronasal thermistor, abdominal accelerometer, transpulmonary electrical impedance, peritracheal microphone, and photoplethysmography) for measuring low respiratory rates in sedated, nonintubated, supine volunteers. A unified approach based on a single breath detection algorithm was applied to each sensor to facilitate comparison. We hypothesized that all of the sensor signals would allow detection of low (<10 breaths per minute) respiratory rates to within ±2 breaths per minute of the reference sensor signal., Methods: Volunteers received remifentanil and propofol infusions at selected target concentration pairs to induce depression of ventilation. Signals from each sensor were analyzed by an identical threshold-based detection algorithm to compute the breathing rate. Bland-Altman limits of agreement and error rate analyses were used to characterize the performance of each sensor compared to the reference sensor., Results: The analysis of the accelerometer and capnometer signals, using Bland-Altman and error rate analyses, showed the highest breath rate agreement (1.96 × standard deviation) of the 7 sensors with -2.1 to 2.2 and -2.5 to 2.7 breaths per minute, respectively. All other signals exhibited wider limits of agreement, with impedance being the widest at -7.8 to 7.4 breaths per minute. For the abdomen accelerometer, 95% of Bland-Altman data points were within ±2 breaths per minute. For the capnometer, 96% of data points were within ±2 breaths per minute. Nasal pressure, thermistor, and microphone all had >80% of data points within ±2 breaths per minute. Impedance and photoplethysmograph signals had 58% and 64%, respectively., Conclusions: A unified approach can be applied to a variety of sensor signals to estimate respiratory rates in spontaneously breathing, nonintubated, sedated volunteers. However, detecting clinically relevant low respiratory rates (<6 breaths per minute) is a technical challenge. By our analysis, no single sensor was able to detect slow respiratory rates with adequate precision (<±2 breaths per minute of the reference signal). Of the sensors evaluated, capnometers and abdominal accelerometers may be the most reliable sensors for identifying hypopnea and central apnea.

Background: In patients who receive a nondepolarizing neuromuscular blocking drug (NMBD) during anesthesia, undetected postoperative residual neuromuscular block is a common occurrence that carries a risk of potentially serious adverse events, particularly postoperative pulmonary complications. There is abundant evidence that residual block can be prevented when real-time (quantitative) neuromuscular monitoring with measurement of the train-of-four ratio is used to guide NMBD administration and reversal. Nevertheless, a significant percentage of anesthesiologists fail to use quantitative devices or even conventional peripheral nerve stimulators routinely. Our hypothesis was that a contributing factor to the nonutilization of neuromuscular monitoring was anesthesiologists' overconfidence in their knowledge and ability to manage the use of NMBDs without such guidance., Methods: We conducted an Internet-based multilingual survey among anesthesiologists worldwide. We asked respondents to answer 9 true/false questions related to the use of neuromuscular blocking drugs. Participants were also asked to rate their confidence in the accuracy of each of their answers on a scale of 50% (pure guess) to 100% (certain of answer)., Results: Two thousand five hundred sixty persons accessed the website; of these, 1629 anesthesiologists from 80 countries completed the 9-question survey. The respondents correctly answered only 57% of the questions. In contrast, the mean confidence exhibited by the respondents was 84%, which was significantly greater than their accuracy. Of the 1629 respondents, 1496 (92%) were overconfident., Conclusions: The anesthesiologists surveyed expressed overconfidence in their knowledge and ability to manage the use of NMBDs. This overconfidence may be partially responsible for the failure to adopt routine perioperative neuromuscular monitoring. When clinicians are highly confident in their knowledge about a procedure, they are less likely to modify their clinical practice or seek further guidance on its use.

Aim: Opioid consumption and addiction are increasing worldwide, yet the USA stands out for its high addiction rates and opioid-related deaths. Considering that patient characteristics are comparable across western countries, physicians' prescribing modalities may influence opioid consumption. We conducted a pilot study to examine opioid-related beliefs and prescription habits of Dutch and American physicians. Methods & materials: A survey was administered to 488 physicians who routinely prescribe opioids for postoperative pain. Results: A total of 75 (16%) physicians responded to the survey. When deciding to prescribe opioids, Dutch physicians adopted a patient-guided approach, whereas most American doctors followed strict guidelines and protocols. Conclusion: This study identified significant differences between Dutch and American physicians' attitudes and prescribing modalities.

Background and Objectives: A common analgesic technique for total knee arthroplasty (TKA) is to inject local anesthetic into the periarticular tissue during surgery, known as local infiltration analgesia (LIA). Since the solution used typically contains a large amount of local anesthetic, concerns arise about exceeding the maximum dosage when adding a peripheral nerve block. Little research exists that addresses serum ropivacaine concentrations following LIA combined with peripheral nerve block. We hypothesized that after combining LIA and adductor canal blockade (ACB), serum ropivacaine concentrations would remain below levels associated with local anesthetic toxicity., Methods: This was a prospective observational study that included 14 subjects undergoing TKA with intraoperative LIA containing 270 mg ropivacaine with epinephrine. Patients weighing less than 80 kg were excluded due to standardized dosing by our pharmacy. Seven patients were assigned consecutively to receive LIA alone (Group LIA) and seven were assigned to receive LIA plus ACB with 100 mg ropivacaine with epinephrine (Group LIA+ACB). Venous serum ropivacaine concentrations were measured over 24 hours., Results: Peak serum concentrations (Cmax) in Group LIA ranged from 0.23 to 0.75 µg/mL and occurred at times from 4 to 24 hours. Cmax in Group LIA+ACB ranged from 0.46 to 1.00 µg/mL and occurred at times from 4 to 8 hours. No participants demonstrated signs or symptoms of local anesthetic toxicity., Conclusions: Total serum concentration of ropivacaine after LIA using 270 mg ropivacaine with and without an additional 100 mg perineural ropivacaine remained well below the toxicity threshold of 3.0 µg/mL at all time points. Additional studies are needed to ascertain the safety of combining LIA with peripheral nerve blockade., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2019. No commercial re-use. See rights and permissions. Published by BMJ.)