Anesthesiology最新文献

{"title":"Digital Disasters: The Growing Threat of Healthcare Ransomware.","authors":"Jeffrey L Tully,Rodney A Gabriel,Ruth S Waterman,Christian J Dameff","doi":"10.1097/aln.0000000000005442","DOIUrl":"https://doi.org/10.1097/aln.0000000000005442","url":null,"abstract":"Healthcare cybersecurity incidents are increasing in frequency and severity. Ransomware, a type of malicious software that results in the encryption of data and systems for financial extortion, often renders computers and networks inaccessible for prolonged periods of time. Clinical workflows, which depend on connected technology such as electronic health records, laboratory systems, and imaging platforms, may be delayed or disrupted in the setting of a ransomware attack. These attacks may adversely affect the care of patients with time-sensitive conditions. The financial impacts to healthcare delivery organizations can be substantial and may be associated with delayed provider payments, regulatory fines, and class action liability. Higher-quality research that characterizes patient outcomes and the development of ransomware-specific emergency response plans are needed to increase cybersecurity resiliency of healthcare systems. Possessing relevant acute care clinical skills and operational expertise, anesthesiologists are well positioned to lead patient safety efforts in this domain.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"113 1","pages":"1005-1008"},"PeriodicalIF":8.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945174","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}

{"title":"Pharmacokinetics and pharmacodynamics of remimazolam for procedural sedation in children and adolescents.","authors":"Pieter J Colin,Lynn H Bichajian,Valentin R Curt,Jeroen V Koomen,Thomas Stöhr,Michel M R F Struys,Keira P Mason","doi":"10.1097/aln.0000000000005560","DOIUrl":"https://doi.org/10.1097/aln.0000000000005560","url":null,"abstract":"BACKGROUND/INTRODUCTIONRemimazolam is not approved for use in pediatric patients. The pharmacokinetics of remimazolam have been reported to be similar to those of adult patients after scaling for body size. This manuscript reports on the pharmacokinetics and pharmacodynamics of pediatric patients aged ≥6 to ≤18 years and a subsequent model-based optimization of the used dosing regimen.METHODS31 patients were included in the trial and stratified across four treatment arms: bolus administration, infusion, bolus + fentanyl or infusion + fentanyl. The University of Michigan Sedation Scale (UMSS) was used to assess the depth of sedation. Blood samples were drawn to measure the concentrations of remimazolam and its metabolite CNS7054. Population pharmacokinetic pharmacodynamic modelling was performed in NONMEM ®.RESULTSA population pharmacokinetic model was developed for remimazolam and CNS7054. The elimination clearance of remimazolam was 0.70 L.min -1.70kg -1. A proportional odds model combined with a simplified Minto model described the observed UMSS well. The EC50 of remimazolam for UMSS ≥3 was 777 ng.ml -1 in the absence of fentanyl, and decreased to 655, 533, and 287 ng/ml for concomitant fentanyl steady-state concentrations of 1, 2, or 4 ng.ml -1, respectively. Simulations confirmed that the studied dosing regimen resulted in 9.2 to 22.0% of patients not reaching UMSS ≥3 at the end of the induction. Model-based optimization resulted in higher per kg dosages and the removal of the maximum allowable dose. Simulations indicated that the percentage of patients achieving UMSS ≥3 can be expected to be high (88% to 97%).CONCLUSIONSThis study has shown that the pharmacokinetics of remimazolam are likely different between children ≥6 years old and adults (after correcting for size). In addition, the exposure-response relationship shows that to effectively use remimazolam for procedural sedation in children ≥6 years, the dosing regimen should be modified to allow for higher remimazolam exposures.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"35 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945180","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}

{"title":"General anesthesia-activated neurons in the central amygdala mediate antinociception: Distinct roles in acute versus chronic phases of nerve injury.","authors":"Junli Zhao,Kenta Furutani,Aidan McGinnis,Joseph P Mathew,Fan Wang,Ru-Rong Ji","doi":"10.1097/aln.0000000000005553","DOIUrl":"https://doi.org/10.1097/aln.0000000000005553","url":null,"abstract":"BACKGROUNDGeneral anesthesia (GA), such as isoflurane, induces analgesia (loss of pain) and loss of consciousness through mechanisms that are not fully understood. A distinct population of GABAergic neurons has been recently identified in the central amygdala (CeA) that can be activated by general anesthesia (CeAGA) and exert antinociceptive functions. In this study, we aim to explore the underlying cellular mechanisms of CeAGA neurons across different phases of nerve injury-induced nociceptive sensitization in mice.METHODSThis study used 107 mice, including 57 males and 50 females. We induced c-Fos activation in their brains using 1.2% isoflurane and validated Fos expression via RNAscope in situ hybridization. Unlike previous studies using the CANE method, we labeled CeAGA neurons (tdTomato+) with the Fos-TRAP2 method. We then performed ex vivo electrophysiological recordings to assess the properties of both Fos-positive/CeAGA neurons and Fos-negative CeA neurons. Using chemogenetic strategy to selectively activate the CeAGA neurons, we investigated pain-like behaviors and associated comorbidities in mice after spared nerve injury (SNI).RESULTSIsoflurane induced robust Fos expression in CeA GABAergic neurons. Electrophysiological recordings in brain slices revealed that compared to Fos-negative CeA neurons, CeAGA neurons had higher excitability and exhibited distinct patterns of action potentials. Chemogenetic activation of Fos-TRAPed CeAGA neurons increased nociceptive thresholds in naïve mice and in mice 2 weeks post-SNI, but demonstrated modest antinociception 8 weeks post-SNI. Finally, Fos-negative CeA neurons, but not CeAGA neurons, exhibited increased excitability in the chronic phase of SNI, which was correlated with a downregulation of K +-Cl - cotransporter-2 (KCC2) in the CeA (sham vs. SNI 8 weeks).CONCLUSIONSThese results validate the antinociceptive power of CeAGA neurons using a different approach. Additionally, we highlight distinct roles of CeAGA neurons in governing physiological pain, acute pain, and the transition to chronic pain through KCC2 dysregulation.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"125 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920989","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}

{"title":"Sugammadex for reversal of neuromuscular blockade in neonates and infants <2 years old: results from a phase IV randomized clinical trial.","authors":"Edith Mensah-Osman,Yuki Mukai,Aobo Wang,Maria Matuszczak,Vera Saldien,Heather Leibensperger,Marcel Speek,Amy Locco,Rebecca Wrishko,Angela Gee,W Joseph Herring","doi":"10.1097/aln.0000000000005535","DOIUrl":"https://doi.org/10.1097/aln.0000000000005535","url":null,"abstract":"BACKGROUNDSugammadex is well-tolerated and effective for reversing neuromuscular blockade (NMB) in adults and children ≥2 years old. There is little information on its use in younger children. The aim of this study was to evaluate the efficacy and tolerability of sugammadex in children under 2 years of age.METHODSPhase IV, randomized, parallel-group, multicenter, clinical trial of sugammadex in participants aged birth to <2 years. Part A was open-label and included pharmacokinetic assessments to determine whether sugammadex dose-adjustment for Part B was necessary based on age. Part B was double-blind and evaluated sugammadex 2 mg/kg and 4 mg/kg. Participants were randomized to: 1) moderate NMB and reversal with 2 mg/kg sugammadex, or 2) moderate NMB and reversal with neostigmine + glycopyrrolate or atropine (hereafter, called neostigmine), or 3) deep NMB and reversal with 4 mg/kg sugammadex. The primary efficacy endpoint was time to neuromuscular recovery (TTNMR). The primary efficacy hypothesis was that sugammadex 2mg/kg would be superior to neostigmine for the reversal of moderate NMB as measured by TTNMR in Part B.RESULTS138 participants aged 1 to 720 days were treated in Parts A+B (sugammadex 2mg/kg n=44, sugammadex 4 mg/kg n=63, neostigmine n=31). Based on pharmacokinetic assessments in Part A, no dose-adjustments for age were needed. In Part B, TTNMR for reversal of moderate NMB was faster with sugammadex 2 mg/kg than neostigmine (median of 1.4 minutes vs 4.4 minutes, hazard ratio = 2.40, 95% CI: 1.37, 4.18; p=0.0002). Sugammadex 4 mg/kg achieved rapid TTNMR for reversal of deep NMB with a median of 1.1 minutes (Parts A+B). The percentage of participants with ≥1 adverse event (Parts A+B) was similar for sugammadex and neostigmine. No deaths, drug-related serious adverse events, or hypersensitivity or anaphylaxis events were reported.CONCLUSIONSIn children <2 years old, sugammadex 2 mg/kg reversed moderate NMB faster than neostigmine, and sugammadex 4 mg/kg rapidly reversed deep NMB. Sugammadex 2 mg/kg and 4 mg/kg were well-tolerated.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"24 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914821","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}

{"title":"Altered Gut Microbiome Composition and Function in Individuals with Complex Regional Pain Syndrome.","authors":"Emmanuel Gonzalez, Tali Sahar, May Haddad, Sylvie Toupin, Ramzi Zioud, Muhammad Zoabi, Lilach Eyal Waldman, Zohar Tal Leshinsky, Maayan Ben Sasson, Vibhu Kumar, Yosefa Marom, Ayelet Midbari, Nicholas J B Brereton, Yoram Shir, Amir Minerbi","doi":"10.1097/ALN.0000000000005435","DOIUrl":"10.1097/ALN.0000000000005435","url":null,"abstract":"<p><strong>Background: </strong>Complex regional pain syndrome is a chronic pain syndrome typically affecting a limb. It is characterized by severe spontaneous and evoked pain, along with vasomotor, autonomic, and motor signs and symptoms. Although dysregulation in several physiologic systems has been suggested in complex regional pain syndrome (CRPS), including aberrant inflammatory and immune responses, vasomotor dysfunction, and nervous system changes, the pathophysiologic mechanisms underlying the syndrome remain elusive. Effective treatment options are also limited. Previous research has highlighted the role of the gut microbiome in chronic pain, prompting us to investigate the composition and function of the gut microbiome in CRPS.</p><p><strong>Methods: </strong>The gut microbiomes of individuals with CRPS to age-, sex-, and ethnicity-matched pain-free control participants were compared using 16S rRNA gene amplification. To minimize environmental confounders, participants were recruited from two geographically independent regions. To explore potential changes in gut bacteria-derived metabolites, targeted metabolomic analysis of feces and plasma was performed. Finally, machine learning algorithms were trained to identify the gut microbiome composition specific to CRPS patients and were tested on a validation cohort.</p><p><strong>Results: </strong>In this study, differential abundance analysis revealed significant differences in several bacterial taxa when comparing 53 CRPS patients to 52 unrelated controls, including alterations in short-chain fatty acid-metabolizing species. Targeted stool and plasma metabolite analysis confirmed differences in fecal and plasma short-chain fatty acid levels between CRPS patients and controls. Notably, the microbiome composition alone allowed accurate classification of patients and controls in a geographically independent test cohort.</p><p><strong>Conclusions: </strong>These findings highlight unique compositional and functional changes in the gut microbiome of individuals with CRPS, thus contributing to the growing body of evidence supporting the role of the gut microbiome in chronic pain syndromes. Furthermore, they pave the way for further studies elucidating the pathophysiology of CRPS and exploring new diagnostic aids and treatment modalities.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555649","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}

{"title":"Effects of the quinone analog, ubiquinone-5, on murine mitochondria and hypnosis.","authors":"Yash R Somnay,Aili Wang,Haeun Lim,Keren K Griffiths,Fereshteh Zandkarimi,Kai Chen,Guang Yang,Andrzej Z Wasilczuk,Max B Kelz,David Larr,Mu Yang,Eva Gil-Iturbe,Anna Moon,Matthias Quick,Richard J Levy","doi":"10.1097/aln.0000000000005549","DOIUrl":"https://doi.org/10.1097/aln.0000000000005549","url":null,"abstract":"BACKGROUNDA functional anesthetic target has long been suspected to reside within mitochondria and disruption of bioenergetic capacity is believed to play a role in the anesthetic response. Unfortunately, the exact mechanism by which changes in mitochondrial target activity result in clinically relevant anesthetic endpoints remains unknown. Here we leveraged knowledge of propofol toxicity to guide drug discovery and uncover a previously unknown pharmacological target within mitochondria. We hypothesized that, like propofol, quinone analogs would interfere with electron transfer, cause excessive proton leak within mitochondria, and induce hypnosis. We tested our hypothesis using the short-chain coenzyme Q (CoQ) analog, ubiquinone-5 (Ub5), and aimed to characterize its anesthetic phenotype in the mouse and elucidate the source of Ub5-induced mitochondrial leak.METHODSAnesthetic phenotype was assessed in vivo in the mouse using behavioral and neurophysiological approaches. We measured biological activity in isolated mitochondria using polarography and spectrophotometry and identified source of proton leak using pharmacological inhibitors, mutant mouse strains, and transport activity assays in proteoliposomes. Finally, we assessed cardiotoxic effects in the isolated-perfused mouse heart ex-vivo.RESULTSCoQ analogs caused uncompensated proton leak in developing cardiomyocyte mitochondria and reversible cardiotoxicity in a manner reminiscent of propofol. Tail vein injection of Ub5 induced short-lived loss of righting, EEG changes consistent with a deep state of anesthesia, and reversible decreases in neuronal calcium transients and mitochondrial membrane potential (ΔΨm) in vivo. Precipitous decline in ΔΨm played a role in Ub5-induced unconsciousness and we identified the aspartate-glutamate carrier, Aralar, as a functional target and source of Ub5-mediated proton leak.CONCLUSIONSThe data indicate that uncompensated mitochondrial proton leak is an important mechanistic contributor to the anesthetic response in addition to electron transport inhibition. These findings advance our understanding of how anesthetics induce hypnosis and lay the foundation for next-generation drug discovery.","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"109 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903085","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}

{"title":"Acetaminophen 5-HT3 Antagonist Interaction: Comment.","authors":"Daniel I Sessler, Aline Reuter Pimenta","doi":"10.1097/ALN.0000000000005339","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005339","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"142 5","pages":"951-952"},"PeriodicalIF":9.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802336","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}

{"title":"Amino Acid Infusion for the Prevention of Acute Kidney Injury: Yet a Debatable Issue.","authors":"Samuel N Heyman, Zaid Abassi","doi":"10.1097/ALN.0000000000005432","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005432","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"142 5","pages":"779-782"},"PeriodicalIF":9.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802340","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}

{"title":"Analgesic Effect of Liposomal Bupivacaine: Comment.","authors":"Meg A Rosenblatt, Rebecca L Johnson","doi":"10.1097/ALN.0000000000005384","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005384","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"142 5","pages":"965-966"},"PeriodicalIF":9.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802342","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}

{"title":"The Day THE Dead Space Died . . .","authors":"Jan F A Hendrickx, Andre M De Wolf","doi":"10.1097/ALN.0000000000005416","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005416","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"142 5","pages":"783-784"},"PeriodicalIF":9.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802366","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}