Pub Date : 2025-12-26DOI: 10.1097/aln.0000000000005920
Anne L Donovan,Ting Guo,Seyedeh Ala Mokhtabad Amrei,Joyce Chang,Jina Sinskey,Oana Maties,Rachel Schwartz
BACKGROUNDSince anesthesiologists report the highest intent to leave academic practice of all specialties, understanding the factors driving attrition is essential to maintaining a robust academic workforce. This study aims to explore how academic anesthesiology faculty at various stages of life define and navigate meaningful, sustainable careers in the context of growing clinical, academic, and personal demands and to identify individual-level strategies for long-term career satisfaction in academic anesthesiology.METHODSVirtual focus groups with faculty representing a range of clinical sub-specialties, academic interests, and career stages and practicing across six diverse clinical sites within an academic anesthesiology department were conducted. Six focus groups were stratified by both career stage and self-identified gender (early-career, mid-career, established-career men and women). Three additional focus groups involved participants who self-selected into one of the following groups: Underrepresented in Medicine, Parents, and Researchers. Due to scheduling constraints, two separate focus groups were held for the established-career men, whereas all other groups were conducted in a single session. Focus groups were audio-recorded, transcribed and de-identified prior to performing an inductive thematic analysis.RESULTSFive themes were identified: (1) Forming a Professional Identity Through Use of a "Purposeful Yes;" (2) Understanding One's Professional Motivators; (3) Integrating Work and Life; (4) Progressing Along a Career Arc; and (5) Overcoming Impostor Phenomenon. Each theme corresponds to one or more questions that can assist faculty members in defining their professional goals, priorities, and values. These questions form the basis of a conceptual framework offered as a practical tool for strategically shaping one's professional efforts, building a mentorship team, and periodically re-evaluating progress toward goals.CONCLUSIONSIn this study, five themes are synthesized into a series of guiding questions that form the basis of a conceptual framework for advancing career fulfillment and retention in academic anesthesiology. Use of a "Purposeful Yes" guided by personal values and motivations allows an individual to strategically shape his or her efforts toward a desirable and sustainable career pathway.
{"title":"Developing a Framework for Career Fulfillment in Academic Anesthesiology: Findings from a Single-Institution Focus Group Study.","authors":"Anne L Donovan,Ting Guo,Seyedeh Ala Mokhtabad Amrei,Joyce Chang,Jina Sinskey,Oana Maties,Rachel Schwartz","doi":"10.1097/aln.0000000000005920","DOIUrl":"https://doi.org/10.1097/aln.0000000000005920","url":null,"abstract":"BACKGROUNDSince anesthesiologists report the highest intent to leave academic practice of all specialties, understanding the factors driving attrition is essential to maintaining a robust academic workforce. This study aims to explore how academic anesthesiology faculty at various stages of life define and navigate meaningful, sustainable careers in the context of growing clinical, academic, and personal demands and to identify individual-level strategies for long-term career satisfaction in academic anesthesiology.METHODSVirtual focus groups with faculty representing a range of clinical sub-specialties, academic interests, and career stages and practicing across six diverse clinical sites within an academic anesthesiology department were conducted. Six focus groups were stratified by both career stage and self-identified gender (early-career, mid-career, established-career men and women). Three additional focus groups involved participants who self-selected into one of the following groups: Underrepresented in Medicine, Parents, and Researchers. Due to scheduling constraints, two separate focus groups were held for the established-career men, whereas all other groups were conducted in a single session. Focus groups were audio-recorded, transcribed and de-identified prior to performing an inductive thematic analysis.RESULTSFive themes were identified: (1) Forming a Professional Identity Through Use of a \"Purposeful Yes;\" (2) Understanding One's Professional Motivators; (3) Integrating Work and Life; (4) Progressing Along a Career Arc; and (5) Overcoming Impostor Phenomenon. Each theme corresponds to one or more questions that can assist faculty members in defining their professional goals, priorities, and values. These questions form the basis of a conceptual framework offered as a practical tool for strategically shaping one's professional efforts, building a mentorship team, and periodically re-evaluating progress toward goals.CONCLUSIONSIn this study, five themes are synthesized into a series of guiding questions that form the basis of a conceptual framework for advancing career fulfillment and retention in academic anesthesiology. Use of a \"Purposeful Yes\" guided by personal values and motivations allows an individual to strategically shape his or her efforts toward a desirable and sustainable career pathway.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"28 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1097/aln.0000000000005905
Michael J Furdyna,Allison A Mootz,Shakthi Venkatachalam,Michael R Mathis,Thomas T Klumpner,Kara G Fields,Mahyar Heydarpour,Jill M Mhyre,Brian T Bateman,Sharon C Reale,
BACKGROUNDPrior studies describe maternal cardiac arrest as a rare and often preventable event, but details of clinical care are limited. Our study sought to delineate the frequency, risk factors, etiology, and management of peripartum, peri-anesthetic maternal cardiac arrest in a large, contemporary US cohort.METHODSIn this observational cohort study using the Multicenter Perioperative Outcomes Group database, we identified anesthetic records for delivery and up to 7 days postpartum for patients aged 15-44 between 2015 and 2022. A screening algorithm using administrative data, anesthetic medications, electronic record concepts, and free-text notations identified potential cases of maternal cardiac arrest. Two independent reviewers conducted manual chart reviews to adjudicate the presence of cardiac arrest and to assess etiology, timing, management, and outcomes. We used descriptive statistics to assess associations between patient characteristics and cardiac arrest.RESULTSAmong 778,102 deliveries across 60 institutions, we identified 87 cardiac arrests during peripartum, peri-anesthetic care, corresponding to a frequency of 11.2 per 100,000 deliveries [95% CI, 9.1,13.8]. The most common etiologies were hemorrhage (40.2%) and amniotic fluid embolism (31.0%); anesthetic complications (e.g., high spinal) accounted for 11.5% of arrests. Most arrests occurred during cesarean deliveries (67.8%). Return of spontaneous circulation was achieved in 77.0% of patients; 67.8% survived to 30 days with a median post-anesthetic hospital length of stay of 6 days. Demographic factors associated with arrest included age ≥40, body mass index ≥40, Black race, and Asian or Pacific Islander race. Clinical factors most strongly associated were pulmonary hypertension, placenta accreta spectrum, ischemic heart disease, and stillbirth. Potential deviations from societal cardiac arrest guidelines were identified in 18.4% of arrests.CONCLUSIONSDuring peripartum anesthetic management in the US, maternal cardiac arrests most commonly arise from hemorrhage and amniotic fluid embolism. Our findings inform efforts to improve peripartum cardiac arrest guideline adherence and hemorrhage management.
{"title":"Frequency and Management of Maternal Peripartum Cardiac Arrest: A Multicenter Retrospective Cohort Analysis.","authors":"Michael J Furdyna,Allison A Mootz,Shakthi Venkatachalam,Michael R Mathis,Thomas T Klumpner,Kara G Fields,Mahyar Heydarpour,Jill M Mhyre,Brian T Bateman,Sharon C Reale, ","doi":"10.1097/aln.0000000000005905","DOIUrl":"https://doi.org/10.1097/aln.0000000000005905","url":null,"abstract":"BACKGROUNDPrior studies describe maternal cardiac arrest as a rare and often preventable event, but details of clinical care are limited. Our study sought to delineate the frequency, risk factors, etiology, and management of peripartum, peri-anesthetic maternal cardiac arrest in a large, contemporary US cohort.METHODSIn this observational cohort study using the Multicenter Perioperative Outcomes Group database, we identified anesthetic records for delivery and up to 7 days postpartum for patients aged 15-44 between 2015 and 2022. A screening algorithm using administrative data, anesthetic medications, electronic record concepts, and free-text notations identified potential cases of maternal cardiac arrest. Two independent reviewers conducted manual chart reviews to adjudicate the presence of cardiac arrest and to assess etiology, timing, management, and outcomes. We used descriptive statistics to assess associations between patient characteristics and cardiac arrest.RESULTSAmong 778,102 deliveries across 60 institutions, we identified 87 cardiac arrests during peripartum, peri-anesthetic care, corresponding to a frequency of 11.2 per 100,000 deliveries [95% CI, 9.1,13.8]. The most common etiologies were hemorrhage (40.2%) and amniotic fluid embolism (31.0%); anesthetic complications (e.g., high spinal) accounted for 11.5% of arrests. Most arrests occurred during cesarean deliveries (67.8%). Return of spontaneous circulation was achieved in 77.0% of patients; 67.8% survived to 30 days with a median post-anesthetic hospital length of stay of 6 days. Demographic factors associated with arrest included age ≥40, body mass index ≥40, Black race, and Asian or Pacific Islander race. Clinical factors most strongly associated were pulmonary hypertension, placenta accreta spectrum, ischemic heart disease, and stillbirth. Potential deviations from societal cardiac arrest guidelines were identified in 18.4% of arrests.CONCLUSIONSDuring peripartum anesthetic management in the US, maternal cardiac arrests most commonly arise from hemorrhage and amniotic fluid embolism. Our findings inform efforts to improve peripartum cardiac arrest guideline adherence and hemorrhage management.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"33 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1097/aln.0000000000005910
Sangwook Jung,Jan-Marino Ramirez,Margaret M Sedensky,Philip G Morgan
BACKGROUNDOne mechanism proposed for anesthetic-induced neurotoxicity (AIN) is elevated neuronal calcium, leading to mitochondrial damage and caspase activation. Increased cytosolic calcium could arise from increased entry or decreased removal. The relative importances of these distinct mechanisms are unknown. Isoflurane inhibits mitochondrial complex I and reduces ATP at presynaptic terminals leading to synaptic quiescence. We hypothesized that mitochondrial inhibition initiates calcium dysregulation in mouse wildtype and mitochondrial mutant neurons, leading to AIN.METHODSPresynaptic calcium levels were monitored using VGlut1-GCaMP5 or an ER-specific GCaMP6 during electrical stimulations of neuronal cultures. Cultures were stimulated in the presence of isoflurane and blockers or activators of calcium removal. Mitochondrial damage was monitored using MitoViewTM. Cleaved caspase induction assessed anesthetic-induced neurotoxicity.RESULTSIn the absence of isoflurane, neuronal stimulation transiently increased presynaptic calcium levels. Isoflurane increased the half-life for calcium decay in wildtype cultures (t(sec)) unexposed, 14(10); exposed, 160(77); p =0.001). Maintaining ATP levels rescued the isoflurane-induced defective removal of calcium (t(sec), 30mM glucose, 16(14), n = 8; p = 0.001). Activation of the sarcoplasmic endoplasmic reticulum calcium ATPase (SERCA) alleviated the isoflurane-induced defective removal of calcium (t(sec), no SERCA activator, 159(78); SERCA activator, 36(18); p =0.002). Similar results were seen for mutant cultures exposed to lower, but equipotent, concentrations of isoflurane. Isoflurane induced a SERCA-dependent decrease in uptake of MitoViewTM and an increase in cleaved caspase in wildtype cultures.CONCLUSIONSIsoflurane causes a failure of SERCA-dependent calcium removal by inhibition of mitochondrial production of ATP. The increase in intracellular calcium leads to early signs of cellular toxicity.
{"title":"The Effects of Isoflurane Inhibition of Mitochondrial Complex I on Calcium Removal in Mouse Neuronal Cultures.","authors":"Sangwook Jung,Jan-Marino Ramirez,Margaret M Sedensky,Philip G Morgan","doi":"10.1097/aln.0000000000005910","DOIUrl":"https://doi.org/10.1097/aln.0000000000005910","url":null,"abstract":"BACKGROUNDOne mechanism proposed for anesthetic-induced neurotoxicity (AIN) is elevated neuronal calcium, leading to mitochondrial damage and caspase activation. Increased cytosolic calcium could arise from increased entry or decreased removal. The relative importances of these distinct mechanisms are unknown. Isoflurane inhibits mitochondrial complex I and reduces ATP at presynaptic terminals leading to synaptic quiescence. We hypothesized that mitochondrial inhibition initiates calcium dysregulation in mouse wildtype and mitochondrial mutant neurons, leading to AIN.METHODSPresynaptic calcium levels were monitored using VGlut1-GCaMP5 or an ER-specific GCaMP6 during electrical stimulations of neuronal cultures. Cultures were stimulated in the presence of isoflurane and blockers or activators of calcium removal. Mitochondrial damage was monitored using MitoViewTM. Cleaved caspase induction assessed anesthetic-induced neurotoxicity.RESULTSIn the absence of isoflurane, neuronal stimulation transiently increased presynaptic calcium levels. Isoflurane increased the half-life for calcium decay in wildtype cultures (t(sec)) unexposed, 14(10); exposed, 160(77); p =0.001). Maintaining ATP levels rescued the isoflurane-induced defective removal of calcium (t(sec), 30mM glucose, 16(14), n = 8; p = 0.001). Activation of the sarcoplasmic endoplasmic reticulum calcium ATPase (SERCA) alleviated the isoflurane-induced defective removal of calcium (t(sec), no SERCA activator, 159(78); SERCA activator, 36(18); p =0.002). Similar results were seen for mutant cultures exposed to lower, but equipotent, concentrations of isoflurane. Isoflurane induced a SERCA-dependent decrease in uptake of MitoViewTM and an increase in cleaved caspase in wildtype cultures.CONCLUSIONSIsoflurane causes a failure of SERCA-dependent calcium removal by inhibition of mitochondrial production of ATP. The increase in intracellular calcium leads to early signs of cellular toxicity.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"54 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1097/aln.0000000000005827
Samuel Castro,Louise Y Sun
As cardiovascular patients live longer and undergo increasingly complex procedures, relying solely on mortality as benchmark of success is no longer sufficient. While patient-reported outcomes incorporate quality of life, symptoms, and functional status, they are often clinician-framed, lengthy, and difficult to integrate into routine care. Patient-defined outcomes is a patient-led evolution of this concept that emphasizes priorities such as autonomy and independence and avoiding outcomes deemed so undesirable that patients would sacrifice longevity to prevent them. Disability-free survival and patient-defined adverse cardiovascular and noncardiovascular events are composite patient-defined outcomes codeveloped with patients. Unlike patient-reported outcomes, which can be unwieldy, patient-defined outcomes are interpretable, autonomy-centered endpoints that extend beyond survival and traditional quality-of-life questionnaires. Integrating these measures into cardiac surgical and interventional workflows, especially during preoperative assessment and tailored optimization, helps align care with patient goals. Patient-defined outcomes have the potential to transform perioperative care by shifting the focus from living longer to living better.
{"title":"Patient-defined Outcomes in Cardiovascular Surgery and Interventions.","authors":"Samuel Castro,Louise Y Sun","doi":"10.1097/aln.0000000000005827","DOIUrl":"https://doi.org/10.1097/aln.0000000000005827","url":null,"abstract":"As cardiovascular patients live longer and undergo increasingly complex procedures, relying solely on mortality as benchmark of success is no longer sufficient. While patient-reported outcomes incorporate quality of life, symptoms, and functional status, they are often clinician-framed, lengthy, and difficult to integrate into routine care. Patient-defined outcomes is a patient-led evolution of this concept that emphasizes priorities such as autonomy and independence and avoiding outcomes deemed so undesirable that patients would sacrifice longevity to prevent them. Disability-free survival and patient-defined adverse cardiovascular and noncardiovascular events are composite patient-defined outcomes codeveloped with patients. Unlike patient-reported outcomes, which can be unwieldy, patient-defined outcomes are interpretable, autonomy-centered endpoints that extend beyond survival and traditional quality-of-life questionnaires. Integrating these measures into cardiac surgical and interventional workflows, especially during preoperative assessment and tailored optimization, helps align care with patient goals. Patient-defined outcomes have the potential to transform perioperative care by shifting the focus from living longer to living better.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"3 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-18DOI: 10.1097/aln.0000000000005906
Lukas M Müller-Wirtz,Orkun Kopac,Adam Esa,Catalina A Dussan Tovar,Mohammad Khudirat,Mehmet Yazar,Alper Gulluoglu,Lu Wang,Kurt Ruetzler,Marcelo Gama de Abreu,Alparslan Turan
BACKGROUNDMechanical power (MP) - the energy transferred to the respiratory system per unit time - has been proposed as an overall indicator of ventilator-related harm. We therefore tested in this post hoc analysis of trial data whether intraoperative mechanical power normalized to predicted bodyweight is associated with impaired oxygenation in the postoperative anesthesia care unit (PACU) or in the ward, PPC, and length of hospital stay.METHODSThe original trial randomly assigned patients having orthopedic surgery to sequential factorial clusters of intraoperative ventilation with tidal volumes of 6 versus 10 ml/kg predicted bodyweight and a PEEP of 5 versus 8 cmH2O, providing a wide range of exposure to mechanical power. We calculated the time-weighted mechanical power normalized to the predicted bodyweight (MP-PBW) for each patient included in the underlying trial and evaluated its association with the time-weighted average SpO2/FiO2 ratio (SF-TWA) during the first hour of PACU stay, SF-TWA in the ward, PPC, and length of hospital stay using a multivariable linear mixed model. We accounted for repeated surgeries and adjusted for demographic and intraoperative characteristics.RESULTSWe included 2,860 surgeries performed in 2,582 patients. Patients were on average 63 years (SD 14), 53% female, 83% Caucasian, had a mean BMI of 31 kg/m2 (SD: 7), and were mainly ASA III (72%). Average MP-PBW was 0.20 J/min/kgPBW (SD: 0.06) and average SF-TWA in PACU was 35341. An 0.1 J/min/kgPBW increment in MP-PBW was associated with a reduction in SF-TWA in PACU by -11 [95%CI: -14, -8] (p<0.001), a reduction in SF-TWA in wards by -8 [-11, -5] (p<0.001), and 55% higher odds of PPC (OR 1.55 [1.05, 2.27], p=0.026). MP-PBW was unrelated to length of hospital stay (OR 1.01 (0.97, 1.05), p=0.68). Models including peak or driving pressures explained nearly the same amount of variance in postoperative oxygenation (marginal R² = 0.207) as the model including MP-PBW (marginal R² = 0.210).CONCLUSIONSHigher intraoperative mechanical power was associated with impaired postoperative oxygenation and pulmonary complications in patients undergoing orthopedic surgery. Driving pressure had a comparable strength of association with postoperative oxygenation.
{"title":"Mechanical power and the association with postoperative impaired oxygenation and pulmonary complications in orthopedic patients: post hoc analysis of a cluster factorial randomized trial.","authors":"Lukas M Müller-Wirtz,Orkun Kopac,Adam Esa,Catalina A Dussan Tovar,Mohammad Khudirat,Mehmet Yazar,Alper Gulluoglu,Lu Wang,Kurt Ruetzler,Marcelo Gama de Abreu,Alparslan Turan","doi":"10.1097/aln.0000000000005906","DOIUrl":"https://doi.org/10.1097/aln.0000000000005906","url":null,"abstract":"BACKGROUNDMechanical power (MP) - the energy transferred to the respiratory system per unit time - has been proposed as an overall indicator of ventilator-related harm. We therefore tested in this post hoc analysis of trial data whether intraoperative mechanical power normalized to predicted bodyweight is associated with impaired oxygenation in the postoperative anesthesia care unit (PACU) or in the ward, PPC, and length of hospital stay.METHODSThe original trial randomly assigned patients having orthopedic surgery to sequential factorial clusters of intraoperative ventilation with tidal volumes of 6 versus 10 ml/kg predicted bodyweight and a PEEP of 5 versus 8 cmH2O, providing a wide range of exposure to mechanical power. We calculated the time-weighted mechanical power normalized to the predicted bodyweight (MP-PBW) for each patient included in the underlying trial and evaluated its association with the time-weighted average SpO2/FiO2 ratio (SF-TWA) during the first hour of PACU stay, SF-TWA in the ward, PPC, and length of hospital stay using a multivariable linear mixed model. We accounted for repeated surgeries and adjusted for demographic and intraoperative characteristics.RESULTSWe included 2,860 surgeries performed in 2,582 patients. Patients were on average 63 years (SD 14), 53% female, 83% Caucasian, had a mean BMI of 31 kg/m2 (SD: 7), and were mainly ASA III (72%). Average MP-PBW was 0.20 J/min/kgPBW (SD: 0.06) and average SF-TWA in PACU was 35341. An 0.1 J/min/kgPBW increment in MP-PBW was associated with a reduction in SF-TWA in PACU by -11 [95%CI: -14, -8] (p<0.001), a reduction in SF-TWA in wards by -8 [-11, -5] (p<0.001), and 55% higher odds of PPC (OR 1.55 [1.05, 2.27], p=0.026). MP-PBW was unrelated to length of hospital stay (OR 1.01 (0.97, 1.05), p=0.68). Models including peak or driving pressures explained nearly the same amount of variance in postoperative oxygenation (marginal R² = 0.207) as the model including MP-PBW (marginal R² = 0.210).CONCLUSIONSHigher intraoperative mechanical power was associated with impaired postoperative oxygenation and pulmonary complications in patients undergoing orthopedic surgery. Driving pressure had a comparable strength of association with postoperative oxygenation.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"29 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1097/aln.0000000000005903
Li Tong,Yong-Xin Guo,Fu-Yang Cao,Shu-Ting Guo,Xin-Yu Hao,Yan-Xiang Li,Zhuo-Ning Zhang,Zhi-Kang Zhou,Yang Li,Yan-Hong Liu,Qiang Fu,Jiang-Bei Cao,Wei-Dong Mi
BACKGROUNDGeneral anesthesia may involve shared neural mechanisms. The periaqueductal gray (PAG) plays a critical role in physiological, instinctive behaviors, as well as sleep-wake regulation. However, the role of the dorsomedial PAG (dmPAG) in regulating the anesthesia-awakening state remains unclear. The study aims to investigate the role of dmPAG glutamatergic neurons in promoting arousal under multiple general anesthetics.METHODSMultiple general anesthetics, including sevoflurane, propofol, ketamine, and dexmedetomidine, were administered to mice of both sexes. Calcium imaging was employed to monitor activity changes in glutamatergic neurons within the dmPAG during anesthesia and arousal. Optogenetic and chemogenetic approaches were used to manipulate neuronal activity and evaluate their effects on anesthesia induction, maintenance, and recovery. Additionally, electroencephalogram (EEG) recordings were analyzed to assess alterations in spectral power and the burst-suppression ratio under anesthesia.RESULTSGlutamatergic neuronal activity in the dmPAG was suppressed during sevoflurane anesthesia but increased during wakefulness, with similar patterns observed for all intravenous anesthetics tested. Optogenetic activation of dmPAG glutamatergic neurons significantly prolonged anesthesia induction time (GFP vs. ChR2, 218.8 ± 50.83 s vs. 372.5 ± 40.18 ;s, P<0.001) and shortened emergence time (GFP vs. ChR2, 230.8 ± 40.44 s vs. 135 ± 19.82 s, P<0.001) under sevoflurane anesthesia. EEG changes characteristic of wakefulness was observed during maintained anesthesia, with the burst suppression ratio decreasing (GFP vs. ChR2: 50.08 ± 8.21% vs. 2.15 ± 3.38%, P<0.001). Chemogenetic activation produced similar effects, while chemogenetic inhibition potentiated the anesthetic effects of all tested anesthetics.CONCLUSIONSThe findings suggest that glutamatergic neurons in the dmPAG may act as a common neural substrate for multiple anesthetic agents, playing a critical role in both the loss and recovery of consciousness.
背景全身麻醉可能涉及共享的神经机制。导水管周围灰质（PAG）在生理、本能行为和睡眠觉醒调节中起着至关重要的作用。然而，背内侧PAG （dmPAG）在调节麻醉-觉醒状态中的作用尚不清楚。本研究旨在探讨dmPAG谷氨酸能神经元在多种全身麻醉下促进觉醒的作用。方法采用七氟醚、异丙酚、氯胺酮、右美托咪定等多种全麻给药。采用钙显像法监测麻醉和觉醒时dmPAG内谷氨酸能神经元的活动变化。采用光遗传学和化学遗传学方法来控制神经元活动，并评估其对麻醉诱导、维持和恢复的影响。此外，分析脑电图（EEG）记录以评估麻醉下频谱功率和突发抑制比的变化。结果七氟醚麻醉时，dmPAG中谷氨酸能神经元的活性被抑制，但在清醒状态下，谷氨酸能神经元的活性增加，所有静脉麻醉药均有类似的模式。光遗传激活dmPAG谷氨酸能神经元显著延长七氟醚麻醉诱导时间（GFP vs ChR2, 218.8±50.83 s vs 372.5±40.18 s， P<0.001）和缩短苏醒时间（GFP vs ChR2, 230.8±40.44 s vs 135±19.82 s， P<0.001）。维持麻醉时脑电图以清醒为特征变化，爆发抑制比降低（GFP vs ChR2: 50.08±8.21% vs 2.15±3.38%，P<0.001）。化学发生激活产生类似的效果，而化学发生抑制增强了所有测试麻醉剂的麻醉效果。结论dmPAG中的谷氨酸能神经元可能是多种麻醉剂的共同神经底物，在意识丧失和恢复中起关键作用。
{"title":"The role of the dorsomedial periaqueductal gray glutamatergic neurons in promoting arousal under multiple general anesthetics in mice.","authors":"Li Tong,Yong-Xin Guo,Fu-Yang Cao,Shu-Ting Guo,Xin-Yu Hao,Yan-Xiang Li,Zhuo-Ning Zhang,Zhi-Kang Zhou,Yang Li,Yan-Hong Liu,Qiang Fu,Jiang-Bei Cao,Wei-Dong Mi","doi":"10.1097/aln.0000000000005903","DOIUrl":"https://doi.org/10.1097/aln.0000000000005903","url":null,"abstract":"BACKGROUNDGeneral anesthesia may involve shared neural mechanisms. The periaqueductal gray (PAG) plays a critical role in physiological, instinctive behaviors, as well as sleep-wake regulation. However, the role of the dorsomedial PAG (dmPAG) in regulating the anesthesia-awakening state remains unclear. The study aims to investigate the role of dmPAG glutamatergic neurons in promoting arousal under multiple general anesthetics.METHODSMultiple general anesthetics, including sevoflurane, propofol, ketamine, and dexmedetomidine, were administered to mice of both sexes. Calcium imaging was employed to monitor activity changes in glutamatergic neurons within the dmPAG during anesthesia and arousal. Optogenetic and chemogenetic approaches were used to manipulate neuronal activity and evaluate their effects on anesthesia induction, maintenance, and recovery. Additionally, electroencephalogram (EEG) recordings were analyzed to assess alterations in spectral power and the burst-suppression ratio under anesthesia.RESULTSGlutamatergic neuronal activity in the dmPAG was suppressed during sevoflurane anesthesia but increased during wakefulness, with similar patterns observed for all intravenous anesthetics tested. Optogenetic activation of dmPAG glutamatergic neurons significantly prolonged anesthesia induction time (GFP vs. ChR2, 218.8 ± 50.83 s vs. 372.5 ± 40.18 ;s, P<0.001) and shortened emergence time (GFP vs. ChR2, 230.8 ± 40.44 s vs. 135 ± 19.82 s, P<0.001) under sevoflurane anesthesia. EEG changes characteristic of wakefulness was observed during maintained anesthesia, with the burst suppression ratio decreasing (GFP vs. ChR2: 50.08 ± 8.21% vs. 2.15 ± 3.38%, P<0.001). Chemogenetic activation produced similar effects, while chemogenetic inhibition potentiated the anesthetic effects of all tested anesthetics.CONCLUSIONSThe findings suggest that glutamatergic neurons in the dmPAG may act as a common neural substrate for multiple anesthetic agents, playing a critical role in both the loss and recovery of consciousness.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"6 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-12DOI: 10.1097/ALN.0000000000005830
Shira Zelber-Sagi, Vikas N O'Reilly-Shah, Ashish K Khanna, Peter Rock, Itay Bentov
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and related advanced fibrosis are associated with poor hepatic and extrahepatic outcomes. However, the role of liver fibrosis in surgery-related mortality remains unclear. The authors aimed to assess the association between a widely used liver fibrosis marker, the Fibrosis-4 (FIB-4) score, and 30-day postoperative mortality and complications.
Methods: A multicenter historical cohort of patients underwent general anesthesia. Data were obtained from the Multicenter Perioperative Outcomes Group dataset. Exclusion criteria included known liver diseases other than MASLD, hepatic failure, and alcohol use disorder. Risk of liver fibrosis was calculated using the FIB-4 score and categorized using the MASLD accepted predefined ranges. Mixed-effects multivariable logistic regression models were built to assess the adjusted conditional odds ratio (cOR) for the primary outcome of mortality and secondary outcomes of acute kidney injury, myocardial injury, and postoperative pulmonary complications.
Results: The final cohort size for the primary outcome of mortality was 1,325,102. Compared to the low-risk FIB-4 category (1.3 or less), the inconclusive FIB-4 category (1.3 to 2.67) was associated with an adjusted cOR of 1.533-fold for mortality (99.75% CI, 1.453 to 1.616), while the elevated category (FIB-4, 2.67 or greater) was associated with an adjusted cOR of 3.765-fold (99.75% CI, 3.572 to 3.969). This association persisted with the application of age-adjusted FIB-4 cutoffs in stratification by age category. A dose-response association was also observed between FIB-4 as a continuous variable and mortality. Among secondary outcomes, elevated FIB-4 was associated with a postoperative cOR of 1.515 for acute kidney injury (99.75% CI, 1.435 to 1.598), a cOR of 1.657 for myocardial injury (99.75% CI, 1.401 to 1.960), and a cOR of 1.323 for postoperative pulmonary complications (99.75% CI, 1.280 to 1.369).
Conclusions: The FIB-4 score is associated with postoperative mortality and complications in a population without clinically apparent liver disease, and evaluation may have value in preoperative patient counseling and optimization.
背景：代谢功能障碍相关的脂肪变性肝病（MASLD）和相关的晚期纤维化与肝脏和肝外预后不良相关。然而，肝纤维化在手术相关死亡率中的作用仍不清楚。我们旨在评估广泛使用的肝纤维化标志物纤维化-4 （FIB-4）评分与术后30天死亡率和并发症之间的关系。方法：对接受全身麻醉的患者进行多中心历史队列研究。数据来自多中心围手术期预后组（MPOG）数据集。排除标准包括已知的除MASLD以外的肝脏疾病、肝功能衰竭和酒精使用障碍。使用FIB-4评分计算肝纤维化风险，并使用MASLD接受的预定义范围进行分类。建立混合效应多变量logistic回归模型，评估死亡率主要结局和急性肾损伤、心肌损伤和术后肺部并发症次要结局的调整条件优势比（cOR）。结果：死亡率主要结局的最终队列大小为1,325,102。与低危FIB-4组（≤1.3）相比，不确定FIB-4组（1.3-2.67）与校正后的死亡率比值为1.533倍[99.75% CI 1.453-1.616]，而高危FIB-4组（≥2.67）与校正后的死亡率比值为3.765倍[99.75% CI 3.572-3.969]。在按年龄分类分层时，使用年龄调整的FIB-4截断值仍然存在这种关联。FIB-4作为一个连续变量与死亡率之间也观察到剂量-反应相关性。在次要结局中，急性肾损伤时FIB-4升高与术后cOR相关，为1.515 [99.75% CI 1.435-1.598]，心肌损伤时cOR为1.657 [99.75% CI 1.401-1.960]，术后肺部并发症时cOR为1.323 [99.75% CI 1.290 -1.369]。结论：FIB-4评分与无临床明显肝病人群的术后死亡率和并发症相关，评估可能对术前患者咨询和优化有价值。
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