Pub Date : 2025-02-01Epub Date: 2025-01-14DOI: 10.1097/ALN.0000000000005273
David O Warner, Randall P Flick
{"title":"Secondary Analyses: The Perils of Making Do.","authors":"David O Warner, Randall P Flick","doi":"10.1097/ALN.0000000000005273","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005273","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"142 2","pages":"263-265"},"PeriodicalIF":9.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977227","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}
Background: Midazolam is a short-acting benzodiazepine frequently used in the perioperative setting. This study aimed to investigate the potential impact of intraoperative midazolam on postoperative delirium in older patients undergoing noncardiac surgery.
Methods: This study included patients aged 65 yr and older who received general anesthesia between April 2020 and April 2022 in multiple hospitals across China. Postoperative delirium occurring within 7 days was assessed using the 3-min Diagnostic Interview for Confusion Assessment Method. Univariable and multivariable logistic regression models based on the random effects were used to determine the association between midazolam administration and the occurrence of postoperative delirium, presented as the risk ratio and 95% CI. A Kaplan-Meier cumulative incidence curve was plotted to compare the distribution of time to postoperative delirium onset between patients who received midazolam and those who did not. Subgroup analyses based on specific populations were performed to explore the relationship between midazolam and postoperative delirium.
Results: In all, 5,663 patients were included, of whom 723 (12.8%) developed postoperative delirium. Univariate and multivariable logistic regression analyses based on random effects of different hospitals showed no significant association between midazolam medication and postoperative delirium among older population (unadjusted risk ratio, 0.96; 95% CI, 0.90 to 1.30; P = 0.38; and adjusted risk ratio, 1.09; 95% CI, 0.91 to 1.33; P = 0.35). The Kaplan-Meier curve showed no difference in the distribution of time to postoperative delirium onset (hazard ratio, 1.02; 95% CI, 0.88 to 1.18; P = 0.82). The results of subgroup analyses found that intraoperative midazolam treatment was not associated with postoperative delirium in the specific subgroups of patients.
Conclusions: Intraoperative administration of midazolam may not be associated with an increased risk of postoperative delirium in older patients undergoing noncardiac surgery.
背景:咪达唑仑是一种短效苯二氮卓类药物,常用于围术期环境。本研究旨在探讨术中使用咪达唑仑对接受非心脏手术的老年患者术后谵妄(POD)的潜在影响:本研究纳入了 2020 年 4 月至 2022 年 4 月期间在中国多家医院接受全身麻醉的年龄≥ 65 岁的患者。采用 3 分钟意识障碍诊断访谈评估法(3D-CAM)对 7 天内发生的 POD 进行评估。基于随机效应的单变量和多变量Logistic回归模型用于确定咪达唑仑用药与POD发生之间的关系,以风险比(RR)和95%置信区间(CI)表示。绘制了 Kaplan-Meier 累计发病率曲线,以比较接受和未接受咪达唑仑治疗的患者之间 POD 发病时间的分布情况。根据特定人群进行了分组分析,以探讨咪达唑仑与 POD 之间的关系:总共纳入了 5,663 名患者,其中 723 人(12.8%)出现了 POD。基于不同医院随机效应的单变量和多变量逻辑回归分析表明,在老年人群中,咪达唑仑用药与 POD 之间无显著关联(未调整 RR=0.96,95% CI:0.90-1.30,P=0.38;调整 RR=1.09,95% CI:0.91-1.33,P=0.35)。卡普兰-梅耶曲线显示,POD发病时间分布无差异(危险比[HR]=1.02,95%CI:0.88-1.18,P=0.82)。亚组分析结果显示,术中咪达唑仑治疗与特定亚组患者的POD无关:结论:在接受非心脏手术的老年患者中,术中使用咪达唑仑可能与 POD 风险增加无关。
{"title":"Effect of Intraoperative Midazolam on Postoperative Delirium in Older Surgical Patients: A Prospective, Multicenter Cohort Study.","authors":"Hao Li, Chang Liu, Yu Yang, Qing-Ping Wu, Jun-Mei Xu, Di-Fen Wang, Jing-Jia Sun, Meng-Meng Mao, Jing-Sheng Lou, Yan-Hong Liu, Jiang-Bei Cao, Chong-Yang Duan, Wei-Dong Mi","doi":"10.1097/ALN.0000000000005276","DOIUrl":"10.1097/ALN.0000000000005276","url":null,"abstract":"<p><strong>Background: </strong>Midazolam is a short-acting benzodiazepine frequently used in the perioperative setting. This study aimed to investigate the potential impact of intraoperative midazolam on postoperative delirium in older patients undergoing noncardiac surgery.</p><p><strong>Methods: </strong>This study included patients aged 65 yr and older who received general anesthesia between April 2020 and April 2022 in multiple hospitals across China. Postoperative delirium occurring within 7 days was assessed using the 3-min Diagnostic Interview for Confusion Assessment Method. Univariable and multivariable logistic regression models based on the random effects were used to determine the association between midazolam administration and the occurrence of postoperative delirium, presented as the risk ratio and 95% CI. A Kaplan-Meier cumulative incidence curve was plotted to compare the distribution of time to postoperative delirium onset between patients who received midazolam and those who did not. Subgroup analyses based on specific populations were performed to explore the relationship between midazolam and postoperative delirium.</p><p><strong>Results: </strong>In all, 5,663 patients were included, of whom 723 (12.8%) developed postoperative delirium. Univariate and multivariable logistic regression analyses based on random effects of different hospitals showed no significant association between midazolam medication and postoperative delirium among older population (unadjusted risk ratio, 0.96; 95% CI, 0.90 to 1.30; P = 0.38; and adjusted risk ratio, 1.09; 95% CI, 0.91 to 1.33; P = 0.35). The Kaplan-Meier curve showed no difference in the distribution of time to postoperative delirium onset (hazard ratio, 1.02; 95% CI, 0.88 to 1.18; P = 0.82). The results of subgroup analyses found that intraoperative midazolam treatment was not associated with postoperative delirium in the specific subgroups of patients.</p><p><strong>Conclusions: </strong>Intraoperative administration of midazolam may not be associated with an increased risk of postoperative delirium in older patients undergoing noncardiac surgery.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":"268-277"},"PeriodicalIF":9.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543234","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}
Pub Date : 2025-02-01Epub Date: 2024-11-05DOI: 10.1097/ALN.0000000000005287
Tilman Gross, Daniel Stehle, Chantal Nagel, Fangyuan Zhou, Emre Duman, Victor Hernandez-Olmos, Rekia Sinderwald, Hannah Gerninghaus, Jonas Petersen, Susanne Feil, Wiebke Kallenborn-Gerhardt, Ruirui Lu, Katharina Metzner, Robert Feil, Ewgenij Proschak, Achim Schmidtko
Background: Emerging evidence indicates that cyclic nucleotide phosphodiesterases exert distinct functions in pain processing and that targeting phosphodiesterases might be a novel strategy for pain relief. This study hypothesized that the phosphodiesterase isoform phosphodiesterase 10A (PDE10A) might be a target for analgesic therapy.
Methods: In situ hybridization, immunostaining, cyclic nucleotide enzyme immunoassays, real-time cyclic guanosine monophosphate imaging, and real-time quantitative reverse transcription polymerase chain reaction were performed to investigate the expression and activity of PDE10A in the dorsal root ganglia and spinal cord. Mice of both sexes were assessed in multiple pain models after the administration of specific PDE10A inhibitors.
Results: PDE10A is distinctly expressed in nociceptive neurons in the dorsal root ganglia and spinal cord of mice. Incubation of cultured sensory neurons with the PDE10A inhibitor, TAK-063 (150 nM), increased cyclic guanosine monophosphate levels in enzyme immunoassays and real-time imaging at the single-cell level. Strikingly, treatment with TAK-063 (0.3 mg/kg intraperitoneal) ameliorated the pain-like behavior of female and male mice in models of acute nociceptive pain after intraplantar injection of capsaicin (mean ± SD, 8.87 ± 8.78 s [TAK-063] vs. 51.24 ± 36.36 s [vehicle], P = 0.020) or allyl isothiocyanate (2.46 ± 3.43 s [TAK-063] vs. 10.36 ± 4.87 s [vehicle]; P = 0.018). Furthermore, TAK-063 (0.3 mg/kg intraperitoneal) reduced established pain-like behavior in models of inflammatory pain induced by intraplantar injection of zymosan (two-way ANOVA, group, F[1,18] = 48.51, TAK-063 vs. vehicle; P ≤ 0.0001) or complete Freund's adjuvant (F[1,14] = 46.10, TAK-063 vs. vehicle; P ≤ 0.0001), without the development of antinociceptive tolerance. The antinociceptive effects were recapitulated using the PDE10A inhibitor PF-2545920.
Conclusions: Collectively, the data support the idea that PDE10A is a suitable target for the development of efficacious analgesic drugs.
背景:新的证据表明,环核苷酸磷酸二酯酶在疼痛处理过程中发挥着不同的功能,以磷酸二酯酶为靶点可能是一种新的镇痛策略。本研究假设磷酸二酯酶同工酶PDE10A可能是镇痛治疗的靶点:方法:通过原位杂交、免疫染色、环核苷酸酶免疫测定、实时环鸟苷酸单磷酸成像和实时定量反转录聚合酶链反应来研究背根神经节和脊髓中 PDE10A 的表达和活性。给小鼠注射特定的 PDE10A 抑制剂后,在多种疼痛模型中对雌雄小鼠进行了评估:结果:PDE10A 在小鼠背根神经节和脊髓的痛觉神经元中明显表达。用PDE10A抑制剂TAK-063(150 nM)诱导培养的感觉神经元,在酶免疫测定和单细胞实时成像中会增加环鸟苷单磷酸的水平。令人震惊的是,在急性痛觉模型中,雌性和雄性小鼠在跖内注射辣椒素后,TAK-063(0.3 mg/kg,腹腔注射)可改善其疼痛样行为(平均值±标度;8.87 ± 8.78 s [TAK-063] vs. 51.24 ± 36.36 s [载体],P = 0.020)或异硫氰酸烯丙酯(2.46 ± 3.43 s [TAK-063] vs. 10.36 ± 4.87 s [载体];P = 0.018)。此外,TAK-063(0.3 毫克/千克,腹腔注射)减少了跖内注射zymosan(双向方差分析,组,F(1,18)= 48.51,TAK-063 vs. 车辆;P ≤ 0.0001)或完全弗氏佐剂(F(1,14)= 46.10,TAK-063 vs. 车辆;P ≤ 0.0001)诱导的炎症性疼痛模型中已建立的疼痛样行为,且不会产生抗痛觉耐受性。使用 PDE10A 抑制剂 PF-2545920 可以重现这种抗痛觉效应:总之,我们的数据支持了 PDE10A 是开发有效镇痛药物的合适靶点这一观点。
{"title":"Inhibition of Phosphodiesterase 10A Alleviates Pain-like Behavior in Mice.","authors":"Tilman Gross, Daniel Stehle, Chantal Nagel, Fangyuan Zhou, Emre Duman, Victor Hernandez-Olmos, Rekia Sinderwald, Hannah Gerninghaus, Jonas Petersen, Susanne Feil, Wiebke Kallenborn-Gerhardt, Ruirui Lu, Katharina Metzner, Robert Feil, Ewgenij Proschak, Achim Schmidtko","doi":"10.1097/ALN.0000000000005287","DOIUrl":"10.1097/ALN.0000000000005287","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence indicates that cyclic nucleotide phosphodiesterases exert distinct functions in pain processing and that targeting phosphodiesterases might be a novel strategy for pain relief. This study hypothesized that the phosphodiesterase isoform phosphodiesterase 10A (PDE10A) might be a target for analgesic therapy.</p><p><strong>Methods: </strong>In situ hybridization, immunostaining, cyclic nucleotide enzyme immunoassays, real-time cyclic guanosine monophosphate imaging, and real-time quantitative reverse transcription polymerase chain reaction were performed to investigate the expression and activity of PDE10A in the dorsal root ganglia and spinal cord. Mice of both sexes were assessed in multiple pain models after the administration of specific PDE10A inhibitors.</p><p><strong>Results: </strong>PDE10A is distinctly expressed in nociceptive neurons in the dorsal root ganglia and spinal cord of mice. Incubation of cultured sensory neurons with the PDE10A inhibitor, TAK-063 (150 nM), increased cyclic guanosine monophosphate levels in enzyme immunoassays and real-time imaging at the single-cell level. Strikingly, treatment with TAK-063 (0.3 mg/kg intraperitoneal) ameliorated the pain-like behavior of female and male mice in models of acute nociceptive pain after intraplantar injection of capsaicin (mean ± SD, 8.87 ± 8.78 s [TAK-063] vs. 51.24 ± 36.36 s [vehicle], P = 0.020) or allyl isothiocyanate (2.46 ± 3.43 s [TAK-063] vs. 10.36 ± 4.87 s [vehicle]; P = 0.018). Furthermore, TAK-063 (0.3 mg/kg intraperitoneal) reduced established pain-like behavior in models of inflammatory pain induced by intraplantar injection of zymosan (two-way ANOVA, group, F[1,18] = 48.51, TAK-063 vs. vehicle; P ≤ 0.0001) or complete Freund's adjuvant (F[1,14] = 46.10, TAK-063 vs. vehicle; P ≤ 0.0001), without the development of antinociceptive tolerance. The antinociceptive effects were recapitulated using the PDE10A inhibitor PF-2545920.</p><p><strong>Conclusions: </strong>Collectively, the data support the idea that PDE10A is a suitable target for the development of efficacious analgesic drugs.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":"332-348"},"PeriodicalIF":9.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581912","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 : 2025-02-01Epub Date: 2025-01-14DOI: 10.1097/ALN.0000000000005234
Robert E Johnstone
{"title":"Telltale Hearts: A Public Health Doctor, His Patients, and the Power of Story.","authors":"Robert E Johnstone","doi":"10.1097/ALN.0000000000005234","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005234","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"142 2","pages":"427-428"},"PeriodicalIF":9.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977242","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 : 2025-02-01Epub Date: 2025-01-14DOI: 10.1097/ALN.0000000000005296
Alicia T Dennis, Annie Xin, Michaela K Farber
Preeclampsia is a common condition of pregnancy characterized by hypertension complicated by cerebral, cardiac, hepatic, renal, hematologic, and placental dysfunction. Patients with preeclampsia frequently undergo cesarean delivery, the most common major surgical procedure in the world. They represent a high-risk perioperative cohort suffering significant preventable morbidity and mortality. This review focuses on the anesthesiologist's role, through a perioperative lens, in reducing maternal complications through management of hypertension and strategies for preserving the function of the brain, heart, liver, kidney, hematologic and coagulation systems, and placenta in patients with preeclampsia undergoing cesarean delivery. Preeclampsia-specific resuscitation, individualized fluid administration, safe neuraxial and general anesthesia, and management of intraoperative bleeding are discussed along with strategies for postoperative analgesia, thromboprophylaxis, and antihypertensive agents in patients who breastfeed. This review discusses recently recognized postoperative deterioration in maternal mental health, the possibility of myocardial injury after cesarean delivery, and the need for long-term cardiometabolic follow-up.
{"title":"Perioperative Management of Patients with Preeclampsia: A Comprehensive Review.","authors":"Alicia T Dennis, Annie Xin, Michaela K Farber","doi":"10.1097/ALN.0000000000005296","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005296","url":null,"abstract":"<p><p>Preeclampsia is a common condition of pregnancy characterized by hypertension complicated by cerebral, cardiac, hepatic, renal, hematologic, and placental dysfunction. Patients with preeclampsia frequently undergo cesarean delivery, the most common major surgical procedure in the world. They represent a high-risk perioperative cohort suffering significant preventable morbidity and mortality. This review focuses on the anesthesiologist's role, through a perioperative lens, in reducing maternal complications through management of hypertension and strategies for preserving the function of the brain, heart, liver, kidney, hematologic and coagulation systems, and placenta in patients with preeclampsia undergoing cesarean delivery. Preeclampsia-specific resuscitation, individualized fluid administration, safe neuraxial and general anesthesia, and management of intraoperative bleeding are discussed along with strategies for postoperative analgesia, thromboprophylaxis, and antihypertensive agents in patients who breastfeed. This review discusses recently recognized postoperative deterioration in maternal mental health, the possibility of myocardial injury after cesarean delivery, and the need for long-term cardiometabolic follow-up.</p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"142 2","pages":"378-402"},"PeriodicalIF":9.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977169","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 : 2025-02-01Epub Date: 2025-01-14DOI: 10.1097/ALN.0000000000005298
Brian O'Gara, Christopher Hughes
{"title":"Volatile Anesthetic Intensive Care Unit Sedation: Reply.","authors":"Brian O'Gara, Christopher Hughes","doi":"10.1097/ALN.0000000000005298","DOIUrl":"https://doi.org/10.1097/ALN.0000000000005298","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"142 2","pages":"424-426"},"PeriodicalIF":9.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977272","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}