Background: Myocardial injury after hip fracture surgery is common and associated with increased mortality. Acute pain is an important risk factor, but whether peripheral nerve block (PNB) could reduce postoperative myocardial injury remains unclear. This study aimed to evaluate the association between single-injection PNB, administered as an adjunct to general or neuraxial anesthesia, and postoperative myocardial injury in high-risk cardiac older adults undergoing hip fracture surgery.
Methods: In this retrospective cohort study, patients aged ≥65 years who underwent hip fracture surgery under general or neuraxial anesthesia between 2012 and 2023 were included. Based on medical records, patients who received a single-injection PNB as an adjunct were assigned to the PNB group; those who did not were assigned to the non-PNB group. The primary outcome was postoperative myocardial injury, defined as any postoperative cardiac troponin measurement exceeding the 99th percentile upper reference limit during the index hospitalization. Confounding effects were adjusted using inverse probability of treatment weighting based on 27 baseline and intraoperative variables. A weighted logistic regression model was used to estimate odds ratio for PNB versus non-PNB groups. Missing data (24.3% of cases) were imputed using multiple imputation.
Results: Data from 1,467 patients were included in the final analysis. Postoperative myocardial injury occurred in 12.0% (96/798) of patients in the PNB group and 21.5% (144/669) in the non-PNB group. The weighted logistic regression analysis showed that single-injection PNB was associated with a significantly lower odds of postoperative myocardial injury (adjusted odds ratio, 0.60; 95% confidence interval, 0.44-0.82; P=0.002).
Conclusions: Single-injection PNB as an adjunct to general or neuraxial anesthesia was associated with a reduced risk of postoperative myocardial injury in high-risk cardiac older adults undergoing hip fracture surgery, possibly through mitigating the link between pain and myocardial injury. Further prospective trials are needed to validate these findings.
{"title":"Association of Peripheral Nerve Block with Postoperative Myocardial Injury in High-Risk Cardiac Older Adults Undergoing Hip Fracture Surgery: A Two-Center Retrospective Cohort Study.","authors":"Hongye Zhang, Jinyu Wu, Dongmei Ni, Yanxia Sun, Yi Ren, Yongsheng Miao, Na Jia, Yuelun Zhang, Zongyang Qu, Dong-Xin Wang, Zhen Hua","doi":"10.1097/ALN.0000000000005921","DOIUrl":"10.1097/ALN.0000000000005921","url":null,"abstract":"<p><strong>Background: </strong>Myocardial injury after hip fracture surgery is common and associated with increased mortality. Acute pain is an important risk factor, but whether peripheral nerve block (PNB) could reduce postoperative myocardial injury remains unclear. This study aimed to evaluate the association between single-injection PNB, administered as an adjunct to general or neuraxial anesthesia, and postoperative myocardial injury in high-risk cardiac older adults undergoing hip fracture surgery.</p><p><strong>Methods: </strong>In this retrospective cohort study, patients aged ≥65 years who underwent hip fracture surgery under general or neuraxial anesthesia between 2012 and 2023 were included. Based on medical records, patients who received a single-injection PNB as an adjunct were assigned to the PNB group; those who did not were assigned to the non-PNB group. The primary outcome was postoperative myocardial injury, defined as any postoperative cardiac troponin measurement exceeding the 99th percentile upper reference limit during the index hospitalization. Confounding effects were adjusted using inverse probability of treatment weighting based on 27 baseline and intraoperative variables. A weighted logistic regression model was used to estimate odds ratio for PNB versus non-PNB groups. Missing data (24.3% of cases) were imputed using multiple imputation.</p><p><strong>Results: </strong>Data from 1,467 patients were included in the final analysis. Postoperative myocardial injury occurred in 12.0% (96/798) of patients in the PNB group and 21.5% (144/669) in the non-PNB group. The weighted logistic regression analysis showed that single-injection PNB was associated with a significantly lower odds of postoperative myocardial injury (adjusted odds ratio, 0.60; 95% confidence interval, 0.44-0.82; P=0.002).</p><p><strong>Conclusions: </strong>Single-injection PNB as an adjunct to general or neuraxial anesthesia was associated with a reduced risk of postoperative myocardial injury in high-risk cardiac older adults undergoing hip fracture surgery, possibly through mitigating the link between pain and myocardial injury. Further prospective trials are needed to validate these findings.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888147","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 : 2025-12-29DOI: 10.1097/aln.0000000000005834
Jordan William Talan,Brian Kaufman,Brendan A McGrath,Mark E Nunnally
{"title":"Management of Out-of-operating room Tracheostomy and Laryngectomy-related Emergencies.","authors":"Jordan William Talan,Brian Kaufman,Brendan A McGrath,Mark E Nunnally","doi":"10.1097/aln.0000000000005834","DOIUrl":"https://doi.org/10.1097/aln.0000000000005834","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"52 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847197","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 : 2025-12-26DOI: 10.1097/aln.0000000000005919
Henrik Lynge Hovgaard,Simon Tilma Vistisen,Johannes Enevoldsen,Frank de Paoli,Rasmus Haarup Lie,Damir Salskov Obad,Peter Carøe Lind,Niels Katballe,Daniel Kjær,Martin R S Jørgensen,Zidryne Karaliunaite,Anni Nørgaard Jeppesen,Linda Riber,Thomas Tw Scheeren
BACKGROUNDOesophagectomy is a key treatment for oesophageal cancer but carries a high risk of postoperative complications, some potentially preventable through optimised haemodynamic management. Goal-directed fluid therapy individualises cardiac output targets but often applies fixed blood pressure thresholds and is discontinued before major postoperative fluid shifts occur. Extending goal-directed fluid therapy into the postoperative period with individualised blood pressure thresholds may address these limitations.METHODSIn this single-centre, prospective, blinded, randomised controlled trial, patients undergoing oesophagectomy were randomised 1:1 to either extended goal-directed fluid therapy or standard care. In the extended goal-directed fluid therapy group, cardiac output was optimised and mean arterial pressure threshold was the individual patient's night-time baseline. The protocol continued from tracheal intubation through to 07:00 the following morning. The primary outcome was total postoperative morbidity, measured by the Comprehensive Complication Index at day 30.RESULTSOf 100 patients (49 extended goal-directed fluid therapy group, 51 standard group), extended goal-directed fluid therapy was associated with a higher fluid balance (2,517 ± 1,194 mL vs 2,001 ± 1,114 mL, mean difference: 516 mL, 95% CI: 57 - 974, p = 0.028), increased norepinephrine use (median: 7,894 μg [IQR: 3,946-13,793] vs 4,611 μg [IQR: 2,138-7,296], p < 0.001), and higher mean arterial pressure (mean difference: 3 mmHg, 95% CI: 1-5, p = 0.011). At day 30, mean Comprehensive Complication Index did not differ between groups (39.0 ± 20.0 vs 39.2 ± 21.0; mean difference: -0.2; 95% CI: -8.6 to 8.1; p = 0.95).CONCLUSIONDespite achieving protocol-driven treatment differences, extended and individualised goal-directed fluid therapy did not reduce postoperative complications following oesophagectomy.
背景食管癌切除术是食管癌的关键治疗方法，但术后并发症的风险很高，一些可能通过优化血流动力学管理来预防。目标导向的液体治疗个体化心输出量目标，但通常采用固定的血压阈值，并在术后发生重大液体转移之前停止。将目标导向的液体治疗扩展到个体化血压阈值的术后期可以解决这些局限性。方法：在这项单中心、前瞻性、盲法、随机对照试验中，接受食管切除术的患者按1:1的比例随机分为延长目标导向液体治疗组或标准治疗组。在扩展目标定向液体治疗组，心输出量得到优化，平均动脉压阈值是个体患者的夜间基线。治疗方案从气管插管一直持续到第二天早上7点。主要终点是术后总发病率，用第30天的综合并发症指数来衡量。结果在100例患者中（扩展目标定向液体治疗组49例，标准组51例），扩展目标定向液体治疗与较高的体液平衡（2,517±1,194 mL vs 2,001±1,114 mL，平均差值：516 mL， 95% CI: 57 - 974, p = 0.028），去甲肾上腺素使用增加（中位数：7,894 μg [IQR: 3,946-13,793] vs 4,611 μg [IQR: 2,138-7,296], p < 0.001），较高的平均动脉压（平均差值：3 mmHg， 95% CI: 1-5, p = 0.011）相关。在第30天，两组患者的平均综合并发症指数无差异（39.0±20.0 vs 39.2±21.0；平均差异：-0.2;95% CI: -8.6 ~ 8.1; p = 0.95）。结论：尽管实现了方案驱动的治疗差异，但延长和个体化目标导向的液体治疗并没有减少食管切除术后的并发症。
{"title":"Individualised Perioperative Blood Pressure and Fluid Therapy in Oesophagectomy a prospective, single-blind randomised controlled trial.","authors":"Henrik Lynge Hovgaard,Simon Tilma Vistisen,Johannes Enevoldsen,Frank de Paoli,Rasmus Haarup Lie,Damir Salskov Obad,Peter Carøe Lind,Niels Katballe,Daniel Kjær,Martin R S Jørgensen,Zidryne Karaliunaite,Anni Nørgaard Jeppesen,Linda Riber,Thomas Tw Scheeren","doi":"10.1097/aln.0000000000005919","DOIUrl":"https://doi.org/10.1097/aln.0000000000005919","url":null,"abstract":"BACKGROUNDOesophagectomy is a key treatment for oesophageal cancer but carries a high risk of postoperative complications, some potentially preventable through optimised haemodynamic management. Goal-directed fluid therapy individualises cardiac output targets but often applies fixed blood pressure thresholds and is discontinued before major postoperative fluid shifts occur. Extending goal-directed fluid therapy into the postoperative period with individualised blood pressure thresholds may address these limitations.METHODSIn this single-centre, prospective, blinded, randomised controlled trial, patients undergoing oesophagectomy were randomised 1:1 to either extended goal-directed fluid therapy or standard care. In the extended goal-directed fluid therapy group, cardiac output was optimised and mean arterial pressure threshold was the individual patient's night-time baseline. The protocol continued from tracheal intubation through to 07:00 the following morning. The primary outcome was total postoperative morbidity, measured by the Comprehensive Complication Index at day 30.RESULTSOf 100 patients (49 extended goal-directed fluid therapy group, 51 standard group), extended goal-directed fluid therapy was associated with a higher fluid balance (2,517 ± 1,194 mL vs 2,001 ± 1,114 mL, mean difference: 516 mL, 95% CI: 57 - 974, p = 0.028), increased norepinephrine use (median: 7,894 μg [IQR: 3,946-13,793] vs 4,611 μg [IQR: 2,138-7,296], p < 0.001), and higher mean arterial pressure (mean difference: 3 mmHg, 95% CI: 1-5, p = 0.011). At day 30, mean Comprehensive Complication Index did not differ between groups (39.0 ± 20.0 vs 39.2 ± 21.0; mean difference: -0.2; 95% CI: -8.6 to 8.1; p = 0.95).CONCLUSIONDespite achieving protocol-driven treatment differences, extended and individualised goal-directed fluid therapy did not reduce postoperative complications following oesophagectomy.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"91 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830321","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 : 2025-12-26DOI: 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}
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