Anesthesiology最新文献

{"title":"Mortality in Hospitalized Patients After Elective and Nonelective Surgery.","authors":"Richard H Epstein, Franklin Dexter, Brenda G Fahy","doi":"10.1097/ALN.0000000000005477","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005477","url":null,"abstract":"<p><strong>Background: </strong>Perioperative death globally has been described as the third leading cause of death behind heart disease and malignant neoplasm and ahead of cerebrovascular disease. However, studies of all-cause perioperative mortality have not distinguished patients who were outpatients preoperatively (\"elective\") from patients having urgent surgery or having surgery on a day after their date of admission (\"nonelective\"). Strategies for reducing overall perioperative mortality are affected by whether most deaths occur after elective or nonelective surgery.</p><p><strong>Methods: </strong>We studied all adult patients undergoing major diagnostic or therapeutic surgery in Florida in 2021 and 2022 hospitalized ≥2 midnights. We compared those who survived to discharge or died between the elective and nonelective groups. Major hospital-acquired complications were considered as sensitivity analyses. The diversity of procedures (ICD-10-PCS codes) was quantified using the inverse of the internal Herfindahl.</p><p><strong>Results: </strong>Among the 1,245,537 hospitalizations studied, the nonelective group accounted for 94.5% (95% CI 94.0-95.1%) of the 20,874 in-hospital deaths (p < 0.0001 vs 50% [\"most\"]). The nonelective group also accounted for most (70.0%) hospitalizations studied. The relative risk of death in the elective vs non-elective group was 0.13 (95% CI 0.12-0.14, p < 0.0001 vs. 1.0). The relative risks of acute kidney injury, hospital-acquired pneumonia, a major adverse cardiovascular event, and infection were all <1.0 in the elective group. Hundreds of different ICD-10-PCS occurred commonly among patients who died, in both groups.</p><p><strong>Conclusions: </strong>Results of previous studies of all-cause perioperative mortality should not be applied to patients having elective major surgery because most deaths (≈95%) and most cases (70%) are in patients having nonelective major surgery (i.e., already admitted to the hospital or undergoing trauma-related surgery). From a public health perspective, interventions to reduce postoperative mortality should be primarily focused on patients who are inpatients before their first major surgical procedure.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727518","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":"Suzetrigine, a Non-Opioid NaV1.8 Inhibitor for Treatment of Moderate-to-Severe Acute Pain: Two Phase 3 Randomized Clinical Trials.","authors":"Todd Bertoch, Dominick D'Aunno, Jessica McCoun, Daneshvari Solanki, Louise Taber, Joshua Urban, Jessica Oswald, Matthew W Swisher, Simon Tian, Xiaopeng Miao, Darin J Correll, Paul Negulescu, Carmen Bozic, Scott G Weiner","doi":"10.1097/ALN.0000000000005460","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005460","url":null,"abstract":"<p><strong>Background: </strong>Opioids are effective for treating acute pain but have safety, tolerability, and addiction concerns while non-opioid analgesics have limited efficacy. Suzetrigine, an oral, non-opioid, small molecule, selectively inhibits the voltage-gated sodium channel 1.8 (NaV1.8) and has potential to provide efficacious and safe relief for acute pain, without addiction concerns.</p><p><strong>Methods: </strong>To evaluate suzetrigine for treatment of acute pain, we conducted two phase 3, randomized, double-blind, placebo- and active-controlled trials in adults with moderate-to-severe acute pain on the verbal categorical rating scale and ≥4 on the numeric pain rating scale (NPRS) after abdominoplasty (N=1118) or bunionectomy (N=1073). After surgery, participants were randomized to suzetrigine (100mg then 50mg every 12hrs), hydrocodone bitartrate/acetaminophen (HB/APAP; 5/325mg every 6hrs), or placebo for 48 hours. The primary endpoint was time-weighted sum of the pain intensity difference in NPRS from 0-48hrs (SPID48) versus placebo. Key secondary endpoints were SPID48 versus HB/APAP and time to ≥2-point reduction in NPRS from baseline versus placebo.</p><p><strong>Results: </strong>The primary endpoint was achieved in both trials with suzetrigine demonstrating statistically significant and clinically meaningful reduction in pain versus placebo. The least squares mean difference in SPID48 between suzetrigine and placebo was 48.4 (95%CI:33.6,63.1;P<0.0001) after abdominoplasty and 29.3 (95%CI:14.0,44.6; P=0.0002) after bunionectomy. Neither trial achieved the first key secondary endpoint of superiority of suzetrigine versus HB/APAP on SPID48. For the second key secondary endpoint of time to ≥2-point reduction in NPRS, suzetrigine had a more rapid onset of clinically meaningful pain relief versus placebo after abdominoplasty (119min versus 480mins, nominal P<0.0001) and bunionectomy (240mins versus 480mins, nominal P=0.0016).Adverse events (AEs) were similar to those seen in post-surgical settings.</p><p><strong>Conclusions: </strong>As compared with placebo, suzetrigine reduced moderate-to-severe acute pain over 48 hours after abdominoplasty or bunionectomy. Pain reduction with suzetrigine was similar to that with HB/APAP. Suzetrigine was associated with adverse events that were mild to moderate in severity.</p><p><strong>Clinicaltrialsgov registration: </strong>NCT05558410 and NCT05553366.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673181","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":"Inhibition of Endoplasmic Reticulum Oxidoreductin 1 modulates neuronal excitability and nociceptive sensitivity in mice.","authors":"Aislinn D Maguire, Shawn M Lamothe, Muhammad Saad Yousuf, Kree Goss, Jayadeep Rao, Gustavo Tenorio, Sridhar R Kaulagari, Lori Hazlehurst, Jason R Plemel, Anna Mw Taylor, Harley T Kurata, Thomas Simmen, Bradley J Kerr","doi":"10.1097/ALN.0000000000005453","DOIUrl":"10.1097/ALN.0000000000005453","url":null,"abstract":"<p><strong>Background: </strong>In the peripheral nervous system, nociceptors become hyperexcitable in both acute and chronic pain conditions. This phenotype can be mediated by dysregulated calcium, which occurs if the endoplasmic reticulum (ER) and mitochondria fail to buffer it appropriately. The redox enzyme endoplasmic reticulum oxidoreductin 1 (ERO1) regulates calcium transfer at ER-mitochondria contact sites (ERMCS). In this study we hypothesized that inhibiting ERO1 and thereby dampening ERMCS calcium transfer might lower nociceptor hyperexcitability in sensory neurons and pain-like behaviours in mice.</p><p><strong>Methods: </strong>C57BL/6 mice were used for histology, behaviour, and cell culture experiments. Behaviour included thermal tail flick, the formalin hind paw injection model of acute inflammatory pain, and hind paw incision post-surgical pain. Post-mortem human dorsal root ganglia (DRGs) were used for immunohistochemistry and in vitro calcium imaging.</p><p><strong>Results: </strong>Here we demonstrate that the α isoform of ERO1 is expressed in mouse dorsal root ganglia (DRGs) across multiple subtypes of mouse sensory neurons. This led us to peripherally administer an ERO1 inhibitor in mice, which acutely reversed nociception in acute inflammatory and post-surgical pain models. We hypothesized that this may be due to reduced excitability of DRG neurons, and tested ERO1 inhibition in vitro. In cultured DRGs, ERO1 inhibition dampened nociceptor excitability and mitochondrial function, suggesting that reduced calcium transfer through ERMCS could be responsible for the behaviour we observed in vivo. We also found ERO1 α expression in human DRGs using immunohistochemistry and previously published single cell RNA sequencing data. Finally, we showed that ERO1 inhibition modulates human sensory neuronal excitability in cultured post-mortem DRGs.</p><p><strong>Conclusions: </strong>We found that ERO1 inhibition dampens mitochondrial function, sensory neuron excitability, and acute pain-like behaviour in mice. Additionally, ERO1 inhibition decreases sensory neuron excitability in post-mortem human sensory neurons in vitro. We propose that targeting ERO1 may be a viable strategy for non-narcotic acute pain relief.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662071","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":"Persistent renal hypoxia and histological changes at 4 weeks after cardiopulmonary bypass in sheep.","authors":"Taku Furukawa, Clive N May, Alemayehu H Jufar, Roger G Evans, Andrew D Cochrane, Bruno Marino, Peter R McCall, Ian E Birchall, Sally G Hood, Jaishankar Raman, Connie P C Ow, Anton Trask-Marino, Rinaldo Bellomo, Lachlan F Miles, Yugeesh R Lankadeva","doi":"10.1097/ALN.0000000000005452","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005452","url":null,"abstract":"<p><strong>Background: </strong>The sustained renal effects of exposure to cardiopulmonary bypass (CPB) are unknown. We aimed to test whether CPB is associated with sustained renal tissue hypoxia and whether such hypoxia is associated with histological injury.</p><p><strong>Methods: </strong>We studied 12 adult female sheep undergoing CPB with a 2-h aortic cross-clamp. We measured systemic and renal hemodynamics and oxygen delivery, kidney function, and renal tissue oxygenation, before and during CPB, in the 48 h after CPB, and weekly for four weeks. We euthanized the sheep at four weeks and obtained renal tissue to perform histopathological assessments for comparison with an independent cohort of five healthy animals that were euthanized without undergoing surgical or experimental interventions. These histological assessments were performed by an independent, treatment-blinded pathologist.</p><p><strong>Results: </strong>Compared with baseline, renal blood flow and renal medullary tissue oxygenation decreased significantly during CPB. In the first 48 h after CPB, there was a continuing significant decrease in medullary tissue oxygenation (from 39.2 ± 13.8 mmHg at baseline to 21.7 ± 16.2 mmHg at 48 h, Ptime = 0.006) with Stage 1 acute kidney injury (AKI) in 42% of animals. Moreover, in the following 4 weeks, medullary (16.1 ± 12.9 mmHg at 4 weeks, Ptime = 0.005) and cortical (17.2 ± 6.5 mmHg at 4 weeks, Ptime = 0.005) tissue oxygenation remained significantly lower than baseline. Finally, compared with healthy sheep, at 4 weeks post-CPB sheep kidneys had significantly more peritubular inflammation (8/8 vs. 1/5, P = 0.007), interstitial fibrosis (6/8 vs. 0/5, P = 0.021) and tubular casts (8/8 vs. 1/5, P = 0.007).</p><p><strong>Conclusions: </strong>Exposure to CPB triggers sustained medullary and cortical tissue hypoxia and is associated with histopathological renal injury. These findings suggest that the renal effect of exposure to CPB may be more profound and longer lasting than currently appreciated.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662108","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":"Association between adherence to patient blood management recommendations and postoperative complications in hip and knee arthroplasty.","authors":"Albert Garcia-Casanovas, Elvira Bisbe, Adria Vizoso, Eugenia Sarsanedas, Anna Garcia-Altes, Maria J Colomina, Marta Barquero, Misericordia Basora","doi":"10.1097/ALN.0000000000005450","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005450","url":null,"abstract":"<p><strong>Background: </strong>Patient blood management (PBM) is a set of evidence-based practices that reduces the need for blood transfusions. However, its impact on relevant clinical outcomes remains unclear. We evaluated the association between adherence to guideline-recommended PBM care and 30-day postoperative complications in patients undergoing primary total knee and hip arthroplasty. Secondary outcomes included the length of hospital stay and red blood cell utilization.</p><p><strong>Methods: </strong>This was a retrospective, multicenter cohort study including patients from 43 hospitals. The PBM clinical pathway comprised nine major guideline-recommended interventions, and adherence was assessed using a composite quality indicator. Multilevel multivariable regression models were used to evaluate the associations between PBM adherence and outcomes at the patient level while accounting for hospital characteristics and hospital variation.</p><p><strong>Results: </strong>A total of 30926 patients who underwent primary total knee or hip arthroplasty between 2016 and 2022 at 43 hospitals were included. Of these, 1335 (4.3%) had 30-day postoperative complications. The median adherence to the PBM clinical pathway was 60.%. Higher PBM adherence was associated with fewer 30-day postoperative complications (adjusted odds ratio, 0.43; 95% confidence interval (CI) 0.32 to 0.58; p < 0.001), including 65% lower odds of major adverse cardiac events and 45% lower odds of infection. Additionally, higher adherence was associated with shorter hospital stays (adjusted incidence rate ratio, 0.77; 95% CI 0.76 to 0.79; p < 0.001) and reduced transfusion rates (adjusted odds ratio, 0.11; 95% CI 0.09 to 0.14; p < 0.001). Sensitivity analyses confirmed these associations.</p><p><strong>Conclusions: </strong>Adherence to the PBM clinical pathway was associated with improved outcomes. While causality cannot be established, these findings support the potential effectiveness of PBM in reducing postoperative complications and its efficiency in shortening hospital stays, beyond minimizing blood transfusions, in patients undergoing knee and hip arthroplasty.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630045","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":"In vitro performance of a charcoal capturing device with desflurane.","authors":"Maurits Hoffmann, Jennifer Jouwena, Andre M De Wolf, Rik Carette, Rinaldo S H Lauwers, Jan F A Hendrickx","doi":"10.1097/ALN.0000000000005445","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005445","url":null,"abstract":"<p><strong>Background: </strong>The use of capturing devices may become required for the continued use desflurane. We tested the percentage of desflurane captured by a charcoal filter (CONTRAfluran)-workstation (Aisys) combination in vitro.</p><p><strong>Methods: </strong>Desflurane in O2/air was administered via an Aisys workstation into a 2 L test lung that was insufflated with CO2 (160 mL/min). First, to confirm all vaporized desflurane reached the capturing device, the amount of desflurane collected in a Douglas bag attached to the machine exhaust was compared to the vaporized amount during 15 min runs with the following fresh gas flow (FGF)//vaporizer setting combinations: (L/min // %): 0.3//8, 0.5//8, 1//6, 2//6, 3//6, 4//6, 5//6, and 6//6. Next, to determine the effect of CO2, the capturing device weight gain was measured with the same FGF ran over 1 hour but without desflurane. Finally, the ratio of the capturing device weight gain / vaporizer weight loss (= performance, expressed in %) was determined for the same 15 min runs with desflurane vaporizer settings described above. All experiments were arbitrarily repeated five times.</p><p><strong>Results: </strong>The amount of vaporized desflurane did not differ from the amount collected in the Douglas bag. When CO2, O2, and air were delivered without desflurane, the capturing device lost a relatively small amount of weight (<5 g), especially with FGF ≤ 1 L/min. Finally, performance with 0.3, 0.5-2 and 3-6L/min FGF was 103, 100, and 95 - 93 %, respectively.</p><p><strong>Conclusions: </strong>CONTRAfluran charcoal filter in vitro performance for desflurane in O2/air combined with the Aisys workstation ranged from 93-103 % with FGF of 0.3 to 3-6 L/min with vaporizer settings that reflect clinical conditions. Defining the place of charcoal filters in clinical practice requires full life cycle analysis of both the charcoal and inhaled agent.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613161","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":"Distinct effects of sevoflurane and propofol on vascular permeability in vitro and in a mouse model.","authors":"Ru Li, Yujie Huang, Kevin Lin, Xuri Li, James P Dilger, Jun Lin","doi":"10.1097/ALN.0000000000005434","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005434","url":null,"abstract":"<p><strong>Background: </strong>General anesthetics may substantially influence endothelium function, potentially affecting outcomes of surgical patients, but their effects are unclear. Here, we studied a commonly used inhaled anesthetic, sevoflurane, and an intravenous anesthetic, propofol, on vascular endothelial permeability using multiple in vitro assays and a mouse model.</p><p><strong>Methods: </strong>Human umbilical vein endothelial cells (HUVECs) and mouse pulmonary endothelial cells (MPECs) were used for in vitro models to test the effect of anesthetics on endothelial permeability. The effect of anesthetics on pulmonary vascular leakage was analyzed using AngioSense® 750 fluorescent tracer and rhodamine-labeled 3-kD dextran in a mouse model. Downstream targets were identified using RNA sequencing and confirmed by qRT-PCR and western blot.</p><p><strong>Results: </strong>Sevoflurane at clinically relevant concentrations disrupted the endothelial monolayer formed by HUVECs and MPECs in transwell permeability models. Sevoflurane, but not propofol, induced 1.8-fold increase of AngioSense® dye accumulation in mouse lung than control, indicating pulmonary vascular leakage in sevoflurane group. RNA sequencing analysis, qRT-PCR, and western blot analysis revealed that sevoflurane induced the expression and activation of hypoxic-induced factor 1α (HIF-1α) in vitro and in vivo. The activation of HIF-1α led to the increased expression of its downstream vascular endothelial growth factor (VEGF). The knockdown of HIF-1α restored the change of endothelial permeability and abolished the increase of VEGF induced by sevoflurane in MPECs.</p><p><strong>Conclusions: </strong>Our results demonstrate that sevoflurane increased endothelial and pulmonary vascular permeability via HIF-1α and VEGF. Propofol had no significant effect on the permeability of endothelium.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555652","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 Jb Brereton, Yoram Shir, Amir Minerbi","doi":"10.1097/ALN.0000000000005435","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005435","url":null,"abstract":"<p><strong>Background: </strong>Complex regional pain syndrome (CRPS) 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 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-, gender- 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 (SCFA) metabolizing species. Targeted stool and plasma metabolite analysis confirmed differences in fecal and plasma SCFA 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":"2025-03-05","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":"EXPLORING THE ADDITIVE OR SYNERGISTIC EFFECTS OF THE SYSTEMIC AND PERINEURAL ROUTES OF DEXAMETHASONE AS ADJUNCTS TO SUPRACLAVICULAR BLOCK: A RANDOMIZED CONTROLLED TRIAL.","authors":"Nasir Hussain, Jarod Speer, Ryan S D'Souza, Marilly Palettas, Mahmoud Abdel-Rasoul, Alberto Uribe, Tristan Weaver, Michael Kushelev, John Coffman, Faraj W Abdallah","doi":"10.1097/ALN.0000000000005433","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005433","url":null,"abstract":"<p><strong>Background: </strong>Both perineural and intravenous dexamethasone have been proposed as effective adjuncts that prolong the duration of peripheral nerve blocks. We sought to explore whether combining systemic with perineural dexamethasone yields any additive or synergistic effect on the characteristics and analgesic effects of peripheral nerve blocks.</p><p><strong>Methods: </strong>Adult patients having distal radius open reduction and internal fixation and/or carpometacarpal arthroplasty under supraclavicular block were randomized to either intravenous dexamethasone; combination of perineural+intravenous dexamethasone; or no dexamethasone (control). Sensory block duration was set as the primary outcome. Secondary outcomes included motor block duration; post-operative rebound pain scores as well as worst pain at 8, 16, 24, 32, 40, and 48-hours; opioid consumption at 0-24 and 25-48 hours; incidence of nausea/vomiting; and presence of burning sensation in the blocked limb at 24 and 48-hours. Our null hypothesis was lack of difference in sensory block duration between the three groups.</p><p><strong>Results: </strong>A total of 104 patients were included in the analysis (37: intravenous dexamethasone; 34: intravenous+perineural dexamethasone; 33: control). Compared to intravenous dexamethasone alone, adding perineural dexamethasone did not yield any incremental benefits in any of the outcomes examined. The mean [SD] of sensory block duration was 21.3 [7.3] hours in the intravenous dexamethasone group, 20.6 [6.1] hours in the perineural+intravenous group, and 16.8 [6.8] hours in the Control group. The mean difference [95% CI] of sensory block duration was significantly prolonged by 4.5 hours [1.3, 7.7] (P=0.006) in intravenous dexamethasone group and 3.4 hours [0.8, 6.8] (P=0.015) in the perineural+intravenous dexamethasone group, when compared to control; however, no difference was observed when the two dexamethasone groups were compared to each other (0.7 hours [-2.5, 3.9](P=0.670)). Compared to control, both intravenous and intravenous+perineural dexamethasone similarly reduced 24-hour pain scores and opioid consumption and decreased incidence of rebound pain.</p><p><strong>Conclusion: </strong>Our findings suggest that intravenous dexamethasone alone is sufficient to improve analgesic outcomes for patients receiving supraclavicular block for upper extremity surgery. Combining the intravenous and perineural dexamethasone routes does not yield additive or synergistic effect on the characteristics and analgesic effects of supraclavicular block.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539994","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 Subanesthetic Oromucosal Dexmedetomidine on Sleep in Humans: A Randomized, Controlled Pharmacokinetics-Pharmacodynamics Study.","authors":"Laura K Schnider, Marta Ratajczak, Rafael Wespi, Jacqueline G Kientsch, Francesco Bavato, Laurenz Marten, Jonas Kost, Maxim Puchkov, Corinne Eicher, Martina Boxler, Clarissa D Voegel, Oliver G Bosch, Eus van Someren, Dario A Dornbierer, Hans-Peter Landolt","doi":"10.1097/ALN.0000000000005314","DOIUrl":"10.1097/ALN.0000000000005314","url":null,"abstract":"<p><strong>Background: </strong>The locus coeruleus noradrenergic system may provide a potential new target for pharmacologic insomnia treatment, particularly in patients suffering from elevated distress. The selective α 2 -noradrenergic agonist dexmedetomidine attenuates locus coeruleus activity in subanesthetic doses, yet no adequate nonparental delivery systems of dexmedetomidine are currently available. To examine the feasibility of oromucosal dexmedetomidine administration, the authors developed two distinct-one sublingual and one buccal-oromucosal, fast-disintegrating dexmedetomidine formulas tailored for self-administration. Here, the authors established the formulas' pharmacokinetic and pharmacodynamic profiles.</p><p><strong>Methods: </strong>In a pilot study (sublingual formulation; n = 8 good sleepers) and a main study (buccal formulation; n = 17 poor sleepers), each following a randomized, double-blind, placebo-controlled crossover design, the authors investigated subanesthetic doses (20 and 40 µg) of the two formulas. They complemented the pharmacokinetic assessments with all-night polysomnography, nocturnal cortisol and melatonin measurements, assessments of cardiovascular functions during and after sleep, cortisol awakening response, and postawakening examination of subjective state and vigilance.</p><p><strong>Results: </strong>Particularly buccal dexmedetomidine was rapidly absorbed and exhibited excellent dose proportionality with minimal between-subject variation in exposure. In poor sleepers, 40 µg buccal dexmedetomidine shortened the sleep latency by 11.5 min, increased the time spent in non-rapid eye movement sleep by 37.2 min, and elevated non-rapid eye movement sleep electroencephalographic slow-wave energy (0.75 to 4.0 Hz) in the first half of the night by roughly 23%. Rapid eye movement sleep latency was dose-dependently prolonged (20 µg, 55.0 min; 40 µg, 115.3 min). Nocturnal cortisol, melatonin and heart rate, and morning cortisol were not significantly affected by dexmedetomidine, nor did postawakening orthostatic regulation, subjective sleepiness and mood, and psychomotor vigilance differ among the conditions.</p><p><strong>Conclusions: </strong>The favorable pharmacokinetic and pharmacodynamic profile of oromucosal dexmedetomidine delivery warrants further dose-finding and clinical studies to establish the exact roles of α 2 receptor agonism in pharmacologic sleep enhancement and as a possible novel mechanism to alleviate stress-related insomnia.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":"476-487"},"PeriodicalIF":9.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}