Akihisa Taguchi, Shinichi Kai, Shino Matsukawa, Hideya Seo, Moritoki Egi
{"title":"Volatile Anesthetic-Induced Skeletal Muscle Atrophy in Mice and Murine-Derived Myotubes: The Role of the Akt Pathway.","authors":"Akihisa Taguchi, Shinichi Kai, Shino Matsukawa, Hideya Seo, Moritoki Egi","doi":"10.1213/ANE.0000000000007466","DOIUrl":"https://doi.org/10.1213/ANE.0000000000007466","url":null,"abstract":"<p><strong>Background: </strong>Volatile anesthetics are gaining attention as sedatives in intensive care units. Sedation is a significant risk factor for skeletal muscle atrophy and weakness in critically ill patients; however, volatile anesthetics' influence on skeletal muscle atrophy remains unclear. Therefore, we investigated their effects on skeletal muscle mass using a murine-derived muscle cell line and mice.</p><p><strong>Methods: </strong>C2C12 myotubes were exposed to isoflurane or sevoflurane. Myotube diameter was assessed using immunofluorescence. The expression levels of Atrogin-1, MuRF1, and LC3-II and phosphorylation levels of p70 S6K and Akt were analyzed to evaluate protein degradation and synthesis. To determine whether these effects were mediated through the Akt pathway, experiments with insulin-like growth factor 1 (IGF-1) were performed. Furthermore, mice skeletal muscle exposed to isoflurane or sevoflurane were compared with control mice and short-term immobility mice induced by sciatic nerve denervation (DN) or hindlimb suspension (HS).</p><p><strong>Results: </strong>Exposure of C2C12 myotubes to 2.8% isoflurane or 5.0% sevoflurane reduced the myotube diameter by 14.4 µm (95% confidential interval [CI], 11.7-17.1, P < .001) and 13.2 µm (95% CI, 10.1-16.2, P < .001), respectively. Exposure to 2.8% isoflurane increased the expressions of Atrogin-1 (2.9-fold [95% CI, 2.1- to 3.8-fold], P < .001), MuRF1 (3.1-fold [95% CI, 2.4- to 3.8-fold], P < .001), and LC3-II (1.6-fold [95% CI, 1.4- to 1.8-fold], P < .001), whereas decreasing phosphorylation of p70 S6K (0.3-fold [95% CI, 0.2- to 0.4-fold], P < .001) and Akt (0.4-fold [95% CI, 0.3- to 0.5-fold], P < .001). Exposure to 5.0% sevoflurane resulted in similar effects. Additionally, IGF-1 counteracted the effects of isoflurane on myotube mass. In mice skeletal muscle, exposure to 1% isoflurane or 1.5% sevoflurane decreased Akt phosphorylation (isoflurane: 0.4-fold [95% CI, 0.1- to 0.8-fold], P = .003; sevoflurane: 0.5-fold [95% CI, 0.4- to 0.6-fold], P = .011) and increased the expression levels of Atrogin-1 (isoflurane: 4.1-fold [95% CI, 3.2- to 5.1-fold], P < .001; sevoflurane: 2.3-fold [95% CI, 1.1- to 3.5-fold], P = .026), MuRF1 (isoflurane: 2.7-fold [95% CI, 1.3- to 4.1-fold], P = .01; sevoflurane: 2.3-fold [95% CI, 1.0- to 3.7-fold], P = .022), and LC3-II (isoflurane: 1.9-fold [95% CI, 0.9- to 3.0-fold], P = .045; sevoflurane: 1.5-fold [95% CI, 1.4- to 1.6-fold], P < .001) while decreasing p70 S6K phosphorylation (isoflurane: 0.5-fold [95% CI, 0.4- to 0.6-fold], P = .013; sevoflurane: 0.7-fold [95% CI, 0.6- to 0.8-fold], P = .008) compared with DN. Similar results were observed when comparing between isoflurane or sevoflurane exposure and HS.</p><p><strong>Conclusions: </strong>Volatile anesthetics induce skeletal muscle atrophy by downregulating the Akt pathway, suggesting they may exacerbate skeletal muscle atrophy beyond immobility effects.</p>","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Artificial Intelligence Supporting Anesthesiology Clinical Decision-Making.","authors":"Rebecca D Minehart, Scott E Stefanski","doi":"10.1213/ANE.0000000000007473","DOIUrl":"https://doi.org/10.1213/ANE.0000000000007473","url":null,"abstract":"","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicholas J Douville, Michael Mathis, Mark E Smolkin, Linda W Martin, Wanda M Popescu, Randal S Blank
{"title":"Inspired Oxygen Concentration During the Re-initiation of Two-Lung Ventilation in Thoracic Surgery: A Post Hoc Analysis of Data From the Multicenter Perioperative Outcomes Group.","authors":"Nicholas J Douville, Michael Mathis, Mark E Smolkin, Linda W Martin, Wanda M Popescu, Randal S Blank","doi":"10.1213/ANE.0000000000007479","DOIUrl":"https://doi.org/10.1213/ANE.0000000000007479","url":null,"abstract":"<p><strong>Background: </strong>A recent multicenter study suggested that the duration of single-lung ventilation, and not the intensity of the hyperoxia (ie, inspired oxygen fraction) during this period, contributes to the development of postoperative pulmonary complications. However, lung reinflation, at the cessation of single-lung ventilation, is a period of particular susceptibility to hyperoxic injury, and the impact of alveolar hyperoxia during this period on postoperative pulmonary complications has not been specifically assessed.</p><p><strong>Methods: </strong>Clinical practice surrounding the inspired oxygen fraction at lung reinflation and potential clinical implications of alveolar hyperoxia occurring during this period were assessed in this secondary analysis of data from a multicenter retrospective cohort study.</p><p><strong>Results: </strong>On multivariable logistic regression, average inspired oxygen fraction during the period of lung reinflation was independently associated with postoperative pulmonary complications (adjusted odds ratio [aOR]: 1.14, 95% confidence interval [CI], 1.01-1.29, P = .032; unit: 10% FiO2 increment). The duration of single-lung ventilation (in hours) also remained significant in this model (aOR: 1.21, 95% CI, 1.03-1.42, P = .020).</p><p><strong>Conclusions: </strong>The results of this study suggest a unique sensitivity to alveolar hyperoxia at the time of lung reinflation and raise the possibility that restricting the inspired oxygen fraction during lung reinflation could reduce injury and related sequelae. Our findings imply that a 10% increase in FiO2 during the reinflation period (eg, increasing FiO2 from 80% to 90%) would be associated with 14% greater odds of developing a postoperative pulmonary complication. However, they should be viewed as hypothesis-generating due to the retrospective nature of the study and serve as justification for prospective investigation of this association.</p>","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mara Serbanescu, Seoho Lee, Fengying Li, Sri Harsha Boppana, Mohamed Elebasy, James R White, C David Mintz
{"title":"Effects of Perioperative Exposure on the Microbiome and Outcomes From an Immune Challenge in C57Bl/6 Adult Mice.","authors":"Mara Serbanescu, Seoho Lee, Fengying Li, Sri Harsha Boppana, Mohamed Elebasy, James R White, C David Mintz","doi":"10.1213/ANE.0000000000007467","DOIUrl":"https://doi.org/10.1213/ANE.0000000000007467","url":null,"abstract":"<p><strong>Background: </strong>Previous work suggests that the gut microbiome can be disrupted by antibiotics, anesthetics, opiates, supplemental oxygen, or nutritional deprivation-all of which are common and potentially modifiable perioperative interventions that nearly all patients are exposed to in the setting of surgery. Gut microbial dysbiosis has been postulated to be a risk factor for poor surgical outcomes, but how perioperative care-independent of the surgical intervention-impacts the gut microbiome, and the potential consequences of this impact have not been directly investigated.</p><p><strong>Methods: </strong>We developed a perioperative exposure model (PEM) in C57Bl/6 mice to emulate the most common elements of perioperative medicine other than surgery, which included 12 hours of nutritional deprivation, 4 hours of volatile general anesthetic, 7 hours of supplemental oxygen, surgical antibiotics (cefazolin), and opioid pain medication (buprenorphine). Gut microbial dynamics and inferred metabolic changes were longitudinally assessed before-and at 3 time points after-PEM by 16S rRNA amplicon sequencing. We then used fecal microbial transplant in secondary abiotic mice to test if, compared to preexposure microbiota, day 3 post-PEM microbial communities affect the clinical response to immune challenge in an endotoxemia model.</p><p><strong>Results: </strong>We observed transient changes in microbiota structure and function after the PEM, including reduced biodiversity, loss of diverse commensals associated with health (including Lactobacillus, Roseburia, and Ruminococcus), and changes in microbiota-mediated amino acid metabolic pathways. Mice engrafted with day 3 post-PEM microbial communities demonstrated markedly reduced survival after endotoxemia compared to those bearing preexposure communities (7-day survival of ~20% vs ~70%, P = .0002).</p><p><strong>Conclusions: </strong>These findings provide the first clear evidence that the combined effects of common perioperative factors, independent of surgery, cause gut microbial dysbiosis and alter the host response to inflammation in the postoperative period.</p>","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ibraheem M Karaye, Dimitry Tumin, Olubukola O Nafiu
{"title":"Beyond the Numbers: Exercising Caution With Interpreting Maternal Outcome Disparities in Coronavirus Disease-2019 Research.","authors":"Ibraheem M Karaye, Dimitry Tumin, Olubukola O Nafiu","doi":"10.1213/ANE.0000000000007483","DOIUrl":"https://doi.org/10.1213/ANE.0000000000007483","url":null,"abstract":"","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yingjie Hu, Jing Xiao, Xiao He, Tingting Qin, Li Wan, Wenlong Yao
{"title":"Comparison of the Learning Curves of Ultrasound-Guided In-Plane Needle Placement Among Four Different Puncture Modes: A Randomized, Crossover, Simulation Study.","authors":"Yingjie Hu, Jing Xiao, Xiao He, Tingting Qin, Li Wan, Wenlong Yao","doi":"10.1213/ANE.0000000000007459","DOIUrl":"https://doi.org/10.1213/ANE.0000000000007459","url":null,"abstract":"<p><strong>Background: </strong>The effects of different positional relationships between the probe, needle, and puncture model on in-plane puncture performance have not been fully evaluated. In this simulation study, we used a 4-period crossover design to compare the learning curves of ultrasound-guided in-plane needle placement among 4 different puncture modes by novices.</p><p><strong>Methods: </strong>Forty residents were randomly assigned to receive training in one of 4 puncture modes according to the placement of the puncture model and the orientation of the probe to the operator: horizontal phantom-parallel probe (HP), horizontal phantom-vertical probe (HV), vertical phantom-parallel probe (VP), and vertical phantom-vertical probe (VV). They were allowed 10 trials on each mode and then received the other 3 trainings following the predefined sequences based on a Williams design. Puncture time was recorded from needle entry until successful in-plane puncture under ultrasound guidance.</p><p><strong>Results: </strong>Linear and generalized linear models indicated significant effects of puncture mode and trial number on puncture time (P < .001 for all models). The mean (standard deviation [SD]) puncture times for 10 trials were 44 (44) s for HP, 37 (34) s for HV, 80 (57) s for VP, and 46 (48) s for VV. HV had the shortest puncture time, while VP had the longest. No significant difference was observed in puncture time between VV and HP modes (P = .330). Within each mode, puncture time significantly decreased from the first to the tenth trial (P = .001 for HP, P < .001 for HV, P < .001 for VP, and P = .002 for VV). VP showed the steepest learning curve; however, even after 10 trials, its puncture time remained significantly higher than that of the other 3 modes (P < .001 for all comparisons).</p><p><strong>Conclusions: </strong>Ultrasound-guided in-plane puncture difficulty follows the order VP > HP = VV > HV.</p>","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Commentary on the Association Between Cerebral Desaturation, Burst Suppression, and Neurological Outcomes in Cardiac Surgery.","authors":"Cheng-Ying Chang, Li-Chung Chen, Cheng-Wei Lu","doi":"10.1213/ANE.0000000000007507","DOIUrl":"https://doi.org/10.1213/ANE.0000000000007507","url":null,"abstract":"","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arthur J Armijo, Brier Fine-Raquet, Nemanja Useinovic, Francesca M Manzella, Vesna Jevtovic-Todorovic, Slobodan M Todorovic
{"title":"Influence of Repeated Exposure to Neonatal Isoflurane on Sleep Architecture and Neuronal Delta and Theta Oscillations in Adolescent Rats.","authors":"Arthur J Armijo, Brier Fine-Raquet, Nemanja Useinovic, Francesca M Manzella, Vesna Jevtovic-Todorovic, Slobodan M Todorovic","doi":"10.1213/ANE.0000000000007462","DOIUrl":"https://doi.org/10.1213/ANE.0000000000007462","url":null,"abstract":"<p><strong>Background: </strong>Normal sleep architecture is important for brain development, and we previously demonstrated that a single exposure to isoflurane during the neonatal period did not induce changes in the sleep architecture and only minimally altered neuronal beta oscillations in adolescent rats. Here, we hypothesized that a more clinically relevant scenario of repeated shorter exposures to isoflurane during brain development may have more profound effects on sleep and wake behavior and associated delta and theta oscillations, respectively.</p><p><strong>Methods: </strong>Male and female rat pups were exposed to sham anesthesia (30% oxygen) or repeated isoflurane delivery for 2 hours each on 3 consecutive days (total exposure of 6 hours). The rat pups were divided into 2 cohorts. In cohort 1, we evaluated the neurotoxic effects of exposure postanesthesia. In cohort 2, electroencephalogram electrodes were implanted into the rat cortex between postnatal days 21-23, and sleep architecture was classified as wake, nonrapid eye movement (NREM), and rapid-eye movement (REM) sleep. Electroencephalogram power spectra were also measured in adolescent rats over a 72-hour period.</p><p><strong>Results: </strong>Isoflurane exposure (n = 11) increased neuroapoptosis to 27. 7 ± 6.5 per mm-2 when compared to the sham group (9. 6 ± 3.0 per mm-2, n = 12, P < .001) and disrupted sleep architecture in adolescent rats. Specifically, there was an increase in the total sleep time (light + dark period) from 89. 9 ± 14.2 minutes in sham group (n = 9) to 111. 2 ± 32.2 minutes in the experimental group (n = 11, P < .05). Furthermore, there were fewer transitions during the dark period from 157. 1 ± 43.3 in sham group (n = 9) to 110. 6 ± 52.5 in the experimental group (n = 11, P < .05). The absolute power of delta oscillations was significantly decreased during the light period of NREM from an average 2217 ± 2016 μV2 in the sham group (n = 8) to 791 ± 659 μV2 in the experimental group (n = 11, P < .05). Further, theta oscillations in the wake stage were significantly decreased in the light period from 1579 ± 885 μV2 in sham group (n = 8) to 690 ± 413 μV2 in the experimental group (n = 11, P < .05) and light + dark period from 1390 ± 808 μV2 in sham group (n = 8) to 691 ± 421 μV2 in the experimental group (n = 11, P < .05).</p><p><strong>Conclusions: </strong>Exposing neonatal rats to isoflurane repeatedly causes significant neurotoxicity, and alters delta and theta thalamocortical oscillations, as well as sleep architecture in adolescence. This contrasts with a single continuous exposure to isoflurane, in which we previously reported no significant effects on sleep-wake architecture and only minimal effect on beta oscillations despite similar acute neurotoxicity.</p>","PeriodicalId":7784,"journal":{"name":"Anesthesia and analgesia","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}