Table of Contents

August 2008

 

CARDIOVASCULAR ANESTHESIOLOGY:

儿童心脏手术人群中抗肝素-血小板因子4抗体的形成的发病率和意义

朱紫瑜 译 陈杰 校

The Incidence and Implications of Anti-Heparin-Platelet Factor 4 Antibody Formation in a Pediatric Cardiac Surgical Population

Mary P. Mullen, David L. Wessel, Kristen C. Thomas, Kimberlee Gauvreau, Ellis J. Neufeld, Francis X. McGowan, Jr, and James A. DiNardo

Anesth Analg 2008 107: 371-378.

心脏手术中抑肽酶和氨甲环酸对血小板功能及术后失血的影响

胡艳译   薛张刚校

The Influence of Aprotinin and Tranexamic Acid on Platelet Function and Postoperative Blood Loss in Cardiac Surgery (Case Report)

Andinet M. Mengistu, Kerstin D. Röhm, Joachim Boldt, Jochen Mayer, Stefan W. Suttner, and Swen N. Piper

Anesth Analg 2008 107: 391-397.

PEDIATRIC ANESTHESIOLOGY:

小儿吸入麻醉诱导期间不良行为依从的预测因子

潘钱玲 译 陈杰 校

Factors Predictive of Poor Behavioral Compliance During Inhaled Induction in Children

Anna M. Varughese, Todd G. Nick, Joel Gunter, Yu Wang, and C. Dean Kurth

Anesth Analg 2008 107: 413-421.

儿童肥大细胞增多症:常规麻醉管理一种复杂疾病

黄凝译  薛张纲校

Pediatric Mastocytosis: Routine Anesthetic Management for a Complex Disease

Melody C. Carter, Ashraf Uzzaman, Linda M. Scott, Dean D. Metcalfe, and Zenaide Quezado

Anesth Analg 2008 107: 422-427.

AMBULATORY ANESTHESIA:

预防性应用止吐药物对呕吐高危患者出院后恶心呕吐发生率及恢复期生活功能性质量的影响:一项前瞻、随机、双盲比较两种预防性止吐方案的试验研究

邱郁薇 译 马皓琳 李士通 校

Antiemetic Prophylaxis for Postdischarge Nausea and Vomiting and Impact on Functional Quality of Living During Recovery in Patients with High Emetic Risks: A Prospective, Randomized, Double-Blind Comparison of Two Prophylactic Antiemetic Regimens

Peter H. Pan, Sherman C. Lee, and Lynne C. Harris

Anesth Analg 2008 107: 429-438.

评价3种不同剂量的帕洛诺司琼与安慰剂在术后72小时内防止术后恶心呕吐的有效性和安全性的随机双盲研究

唐亮 译  马皓琳 李士通 校

A Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Three Different Doses of Palonosetron Versus Placebo in Preventing Postoperative Nausea and Vomiting Over a 72-Hour Period

Anthony L. Kovac, Leopold Eberhart, Jan Kotarski, Giuseppina Clerici, Christian Apfel, and The Palonosetron 04-07 Study Group

Anesth Analg 2008 107: 439-444.

一项随机双盲研究:评估三种不同剂量帕洛诺司琼与安慰剂对预防术后恶心呕吐有效性安全性

陶颖莹 译 陈杰 校

A Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Three Different Doses of Palonosetron Versus Placebo for Preventing Postoperative Nausea and Vomiting

Keith A. Candiotti, Anthony L. Kovac, Timothy I. Melson, Giuseppina Clerici, Tong Joo Gan, and The Palonosetron 04–06 Study Group

Anesth Analg 2008 107: 445-451.

当前止吐方案对高危病人影响的前瞻性研究

蒋宗明译 薛张纲校

The Impact of Current Antiemetic Practices on Patient Outcomes: A Prospective Study on High-Risk Patients

Paul F. White, Jerome F. O'Hara, Charles R. Roberson, Ronald H. Wender, Keith A. Candiotti, and The POST-OP Study Group

Anesth Analg 2008 107: 452-458.

病人危险因素与其术后早期以及后期发生呕吐症状的相关性分析

吴进 译  马皓琳 李士通 校

The Relationship Between Patient Risk Factors and Early Versus Late Postoperative Emetic Symptoms

Paul F. White, Ozlem Sacan, Nina Nuangchamnong, Tiffany Sun, and Matthew R. Eng

Anesth Analg 2008 107: 459-463.

ANESTHETIC PHARMACOLOGY:

帕诺斯琼在分子水平与5-羟色胺受体间独特的相互作用

周姝婧 陈杰

Palonosetron Exhibits Unique Molecular Interactions with the 5-HT3 Receptor

Camilo Rojas, Marigo Stathis, Ajit G. Thomas, Edward B. Massuda, Jesse Alt, Jie Zhang, Ed Rubenstein, Silvia Sebastiani, Sergio Cantoreggi, Solomon H. Snyder, and Barbara Slusher

Anesth Analg 2008 107: 469-478.

联合吸入性麻醉药之间对小鼠的最低肺泡浓度并不起到协同作用

刘沁译 薛张纲校

Inhaled Anesthetics Do Not Combine to Produce Synergistic Effects Regarding Minimum Alveolar Anesthetic Concentration in Rats

Edmond I. Eger, II, Michael Tang, Mark Liao, Michael J. Laster, Ken Solt, Pamela Flood, Andrew Jenkins, Douglas Raines, Jan F. Hendrickx, Steven L. Shafer, Tanifuji Yasumasa, and James M. Sonner

Anesth Analg 2008 107: 479-485.

全麻药对三种配体门控的离子通道有相加作用

黄施伟 译,马皓琳 李士通 校

General Anesthetics Have Additive Actions on Three Ligand Gated Ion Channels

Andrew Jenkins, Ingrid A. Lobo, Diane Gong, James R. Trudell, Ken Solt, R. Adron Harris, and Edmond I. Eger, II

Anesth Analg 2008 107: 486-493.

协同作用是普遍规律?关于产生催眠和肢体活动消失的麻醉药相互作用的综述

潘方立 译 陈杰 校

Is Synergy the Rule? A Review of Anesthetic Interactions Producing Hypnosis and Immobility

Jan F. A. Hendrickx, Edmond I. Eger, II, James M. Sonner, and Steven L. Shafer

Anesth Analg 2008 107: 494-506.

麻醉药相互协同作用:一项对麻醉机连接的理论分析

刘婷洁译 薛张纲校

Additivity Versus Synergy: A Theoretical Analysis of Implications for Anesthetic Mechanisms

Steven L. Shafer, Jan F. A. Hendrickx, Pamela Flood, James Sonner, and Edmond I. Eger, II

Anesth Analg 2008 107: 507-524.

成人肌肉乙酰胆碱受体的成对竞争性拮抗剂之间的协同作用

黄丽娜 译 马皓琳 李士通 校

Synergy Between Pairs of Competitive Antagonists at Adult Human Muscle Acetylcholine Receptors

Man Liu and James P. Dilger

Anesth Analg 2008 107: 525-533.

异丙酚对肝L02细胞的保护作用,激活细胞外信号调节激酶通路减少因过氧化氢引起的细胞凋亡

怀晓蓉 译 陈杰 校

Propofol Protects Hepatic L02 Cells from Hydrogen Peroxide-Induced Apoptosis via Activation of Extracellular Signal-Regulated Kinases Pathway
Hao Wang, Zhanggang Xue, Qiong Wang, Xiaochen Feng, and Zonghou Shen

Anesth Analg 2008 107: 534-540.

TECHNOLOGY, COMPUTING, AND SIMULATION:

使用神经导航仪时六种脉搏氧饱和度仪的表现

秦敏菊译 薛张纲校

The Performance of Six Pulse Oximeters in the Environment of Neuronavigation

Alexander M. Mathes, Sascha Kreuer, Sven O. Schneider, Stephan Ziegeler, and Ulrich Grundmann

Anesth Analg 2008 107: 541-544.

听觉诱发电位的卡嗒声对双频谱指数和熵的影响

姜旭晖译,马皓琳 李士通校

The Effects of Auditory Evoked Potential Click Sounds on Bispectral Index and Entropy

Tomoki Nishiyama

Anesth Analg 2008 107: 545-548.

PATIENT SAFETY:

冠状动脉支架:第一部分 经皮冠状动脉介入治疗的进展

赵嫣红 译 陈杰 校

Coronary Artery Stents: Part I. Evolution of Percutaneous Coronary Intervention (Review Article)

Lisa T. Newsome, Michael A. Kutcher, and Roger L. Royster

Anesth Analg 2008 107: 552-569.

冠状动脉支架:II 围手术期思考与处理

施颖译 薛张纲校

Coronary Artery Stents: II. Perioperative Considerations and Management (Review Article)

Lisa T. Newsome, Robert S. Weller, J. C. Gerancher, Michael A. Kutcher, and Roger L. Royster

Anesth Analg 2008 107: 570-590.

死后的生命:围术期灾祸的后果

唐李隽    马皓琳  李士通 校

Life After Death: The Aftermath of Perioperative Catastrophes (Review Article)

Farnaz M. Gazoni, Marcel E. Durieux, and Lynda Wells

Anesth Analg 2008 107: 591-600.

CRITICAL CARE AND TRAUMA:

胸内血容指数可作为评估急性循环衰竭危重病人机体容量反应的一个指标:与中心静脉压的比较

叶乐 译 陈杰 校

The Intrathoracic Blood Volume Index as an Indicator of Fluid Responsiveness in Critically Ill Patients with Acute Circulatory Failure: A Comparison with Central Venous Pressure

Laurent Muller, Guillaume Louart, Christian Bengler, Pascale Fabbro-Peray, Julie Carr, Jacques Ripart, Jean-Emmanuel de La Coussaye, and Jean-Yves Lefrant

Anesth Analg 2008 107: 607-613.

心脏手术后无创通气结合肺复张疗法的肺部效应

孙鹏飞译 薛张纲校

Pulmonary Effects of Noninvasive Ventilation Combined with the Recruitment Maneuver After Cardiac Surgery

Serdar Celebi, Özge Köner, Ferdi Menda, Oguz Omay, Ilhan Günay, Kaya Suzer, and Nahit Cakar

Anesth Analg 2008 107: 614-619.

OBSTETRIC ANESTHESIOLOGY:

阴部神经阻滞用于会阴切开术后疼痛缓解的随机对照研究

黄佳佳译,马皓琳 李士通校

A Randomized Controlled Trial of Pudendal Nerve Block for Pain Relief After Episiotomy

Younès Aissaoui, Rémi Bruyère, Hassan Mustapha, Dominique Bry, Noureddine Drissi Kamili, and Chantal Miller

Anesth Analg 2008 107: 625-629.

ECONOMICS, EDUCATION, AND POLICY:

随机药物抽检减少麻醉住院医师药物依赖发生率:来自一个研究方案的初步结果

丁俊云 译 陈杰 校

Random Drug Testing to Reduce the Incidence of Addiction in Anesthesia Residents: Preliminary Results from One Program (Special Article)

Michael G. Fitzsimons, Keith H. Baker, Edward Lowenstein, and Warren M. Zapol

Anesth Analg 2008 107: 630-635.

NEUROSURGICAL ANESTHESIOLOGY:

关于在区域麻醉下接受颈动脉内膜剥脱术患者认知功能障碍的研究

夏俊明译 薛张纲校

A Study of Cognitive Dysfunction in Patients Having Carotid Endarterectomy Performed with Regional Anesthesia

Eric J. Heyer, Mark I. Gold, E. Will Kirby, Joseph Zurica, Elizabeth Mitchell, Hadi J. Halazun, Lauren Teverbaugh, Robert R. Sciacca, Robert A. Solomon, Donald O. Quest, Thomas S. Maldonado, Thomas S. Riles, and E. Sander Connolly, Jr

Anesth Analg 2008 107: 636-642.

右美托咪定静脉给药减少大鼠颅内高压引起的肺通透性

朱 慧译 马皓琳 李士通校

Intravenous Dexmedetomidine Decreases Lung Permeability Induced by Intracranial Hypertension in Rats

Motoi Kumagai, Takashi Horiguchi, Toshiaki Nishikawa, Yoko Masaki, and Yoshitugu Tobe

Anesth Analg 2008 107: 643-647.

GENERAL ARTICLES:

3-甲基巴豆酰辅酶A羧化酶缺乏症病人的麻醉

杜唯佳 译 陈杰 校

Anesthetic Management of a Patient with 3-Methylcrotonyl-CoA Carboxylase Deficiency (Case Report)

Karen A. Robbins and Elias N. León-ruiz

Anesth Analg 2008 107: 648-650.

ANALGESIA:

使用帕瑞考昔钠20mg一天两次的多日用药法能减轻全髋置换术后的疼痛

宣丽真译 薛张纲校

A Multiple-Day Regimen of Parecoxib Sodium 20 mg Twice Daily Provides Pain Relief After Total Hip Arthroplasty

Eugene R. Viscusi, Joseph S. Gimbel, Andreas M. Halder, Michael Snabes, Mark T. Brown, and Kenneth M. Verburg

Anesth Analg 2008 107: 652-660.

在特别1点上的针压法对插针主观和自主反应的影响

彭中美 译 马皓琳 李士通 校

The Effect of Acupressure at the Extra 1 Point on Subjective and Autonomic Responses to Needle Insertion

Young-Chang P. Arai, Takahiro Ushida, Tomoaki Osuga, Takako Matsubara, Kahori Oshima, Kana Kawaguchi, Chiaki Kuwabara, Sigeya Nakao, Atsushi Hara, Chihiro Furuta, Erina Aida, Shugyoku Ra, Yui Takagi, and Kyoko Watakabe

Anesth Analg 2008 107: 661-664.

乳癌术后病人自控椎旁镇痛的可行性:两种方法的前瞻性、随机双盲研究的比较

舒慧刚 译 陈杰 校

The Feasibility of Patient-Controlled Paravertebral Analgesia for Major Breast Cancer Surgery: A Prospective, Randomized, Double-Blind Comparison of Two Regimens (Brief Report)

Jennifer McElwain, Noelle M. Freir, Crina L. Burlacu, Denis C. Moriarty, Daniel I. Sessler, and Donal J. Buggy

Anesth Analg 2008 107: 665-668.

咪达唑仑在关节镜膝盖手术以后镇痛的剂量-效果研究

章一静译 薛张纲校

A Dose-Ranging Study of Intraarticular Midazolam for Pain Relief After Knee Arthroscopy (Brief Report)

Yatindra Kumar Batra, Rajesh Mahajan, Sushil Kumar, Subramanyam Rajeev, and Mandeep Singh Dhillon

Anesth Analg 2008 107: 669-672.

调控钙内流可以调节大鼠背根神经节细胞膜兴奋性

张莹译  马皓琳 李士通校

Modulators of Calcium Influx Regulate Membrane Excitability in Rat Dorsal Root Ganglion Neurons

Philipp Lirk, Mark Poroli, Marcel Rigaud, Andreas Fuchs, Patrick Fillip, Chun-Yuan Huang, Marko Ljubkovic, Damir Sapunar, and Quinn Hogan

Anesth Analg 2008 107: 673-685.

长时使用吗啡损害小鼠血管形成和内皮原细胞的活动

刘世文 译 陈杰 校

Prolonged Use of High-Dose Morphine Impairs Angiogenesis and Mobilization of Endothelial Progenitor Cells in Mice

Chen-Fuh Lam, Pei-Jung Chang, Yu-Sheng Huang, Yen-Hui Sung, Chien-Chi Huang, Ming-Wei Lin, Yen-Chin Liu, and Yu-Chuan Tsai

Anesth Analg 2008 107: 686-692.

鞘内注射可乐定可以抑制小鼠脊髓背侧脚神经元的N-甲基-D-天门冬氨酸受体NR1磷酸化引起的神经性疼痛

陈珺珺译 薛张纲校

Intrathecal Clonidine Suppresses Phosphorylation of the N-Methyl-D-Aspartate Receptor NR1 Subunit in Spinal Dorsal Horn Neurons of Rats with Neuropathic Pain

Dae-Hyun Roh, Hyun-Woo Kim, Seo-Yeon Yoon, Hyoung-Sig Seo, Young-Bae Kwon, Ho-Jae Han, Alvin J. Beitz, and Jang-Hern Lee

Anesth Analg 2008 107: 693-700.

不同浓度及容量的局麻药行连续腘窝坐骨神经阻滞的效果:一项双中心、随机、对照研究

裘毅敏译,马皓琳、李士通校

The Effects of Varying Local Anesthetic Concentration and Volume on Continuous Popliteal Sciatic Nerve Blocks: A Dual-Center, Randomized, Controlled Study

Brian M. Ilfeld, Vanessa J. Loland, J. C. Gerancher, Anupama N. Wadhwa, Elizabeth M. Renehan, Daniel I. Sessler, Jonathan J. Shuster, Douglas W. Theriaque, Rosalita C. Maldonado, Edward R. Mariano For the PAINfRETM Investigators

Anesth Analg 2008 107: 701-707.

影响局麻药在硬膜外麻醉神经阻滞平面的因素及腰段和胸段硬膜外麻醉的比较

张磊 译 陈杰 校

Factors Affecting the Distribution of Neural Blockade by Local Anesthetics in Epidural Anesthesia and a Comparison of Lumbar Versus Thoracic Epidural Anesthesia (Review Article)

W. Anton Visser, Ruben A. Lee, and Mathieu J. M. Gielen

Anesth Analg 2008 107: 708-721.

心脏手术中抑肽酶和氨甲环酸对血小板功能及术后失血的影响

The influence of aprotinin and tranexamic acid on platelet function and postoperative blood loss in cardiac surgery.

Andinet M. Mengistu, Kerstin D. Röhm, Joachim Boldt, Jochen Mayer, Stefan W. Suttner, and Swen N. Piper

Department of Anesthesiology and Intensive Care Medicine, Klinikum Ludwigshafen, Bremserstrasse 79, D-67063 Ludwigshafen, Germany. a.mengistu@gmx.de

Anesth Analg 2008 107: 391-397.

 

背景:当前抗纤维蛋白溶解的药物,包括抑肽酶和氨甲环酸被用于心脏手术,通过对血小板不同的作用来减少术后的出血及输血需求。所以我们通过评估体外循环和心脏手术后的血小板功能来确定抑肽酶及氨甲环酸的作用。

方法:在一个随机的前瞻性研究中,对50位择期行体外循环心脏手术病人进行研究。25位接受高剂量的抑肽酶,25位接受高剂量的氨甲环酸。术前,体外循环后,术后3小时,24小时用改良的血栓弹性描记法和全血集合度测定来评价凝血及血小板功能。

结果:与术前相比,体外循环后两组的凝血的功能均受到损害(P < 0.01)。与改良的血栓弹性描记法的测定结果不同,体外循环后,使用氨甲环酸的病人的凝血酶受体介导的集合度有明显的下降(P < 0.05)。与使用氨甲环酸组相比,使用抑肽酶的患者的胸管引流量明显减少(575 mL +/- 228 vs 1033 mL +/- 647, P < 0.05),术后的输血需求明显下降(P < 0.01)。

结论:使用全血集合度测定血小板功能显示抑肽酶和氨甲环酸能减少体外循环后最初24小时内的出血。

(胡艳译   薛张刚校)

BACKGROUND: Antifibrinolytic drugs including aprotinin and tranexamic acid are currently used in cardiac surgery to reduce postoperative bleeding and transfusion requirements, and may have different effects on platelets. We therefore evaluated platelet function after cardiopulmonary bypass (CPB) and cardiac surgery to determine the effect of either aprotinin or tranexamic acid.

METHODS: In a prospective, randomized study, 50 patients scheduled for elective cardiac surgery with CPB were evaluated. Patients received high-dose aprotinin (n = 25) or tranexamic acid (n = 25) as antifibrinolytic drugs. Coagulation and platelet function were assessed preoperatively, after CPB, 3 and 24 h after surgery using modified thrombelastography and whole blood aggregometry.

RESULTS: Impaired coagulation after CPB occurred in both groups compared with preoperative data (P < 0.01). In contrast to modified thrombelastography, thrombin receptor-mediated aggregometry after CPB was significantly decreased only in those patients receiving tranexamic acid until the end of the study period in comparison to the aprotinin group (P < 0.05). Aprotinin-treated patients showed significantly less chest tube drainage (575 mL +/- 228 vs 1033 mL +/- 647, P < 0.05) and need for postoperative transfusion requirements (P < 0.01) compared with the tranexamic acid group.

CONCLUSIONS: Platelet function measured by whole blood aggregometry is better preserved by aprotinin than tranexamic acid and may be responsible for producing less bleeding within the first 24 h after CPB.

 

 

儿童肥大细胞增多症:常规麻醉管理一种复杂疾病

Pediatric mastocytosis: routine anesthetic management for a complex disease.

Melody C. Carter, Ashraf Uzzaman, Linda M. Scott, Dean D. Metcalfe, and Zenaide Quezado

Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr. MSC 1881, Bldg 10 Room 11C-213, Bethesda, MD 20892, USA.

Anesth Analg 2008 107: 422-427

 

背景:儿童肥大细胞增多症包括一系列临床变种,具有多器官系统内固有肥大细胞数目增多的特征。肥大细胞在介导过敏反应方面起作用,肥大细胞增多症患者易发生有或无刺激的过敏反应发作。

方法:调查自1993年至2006年为诊断或外科手术接受麻醉的儿童肥大细胞增多症患者的围麻醉期记录,同时进行有关儿童肥大细胞增多症麻醉经验的文献回顾。

结果:行麻醉时平均年龄为3.2岁(年龄6个月-20岁)的22名儿童肥大细胞增多症患者,29次为诊断或外科手术接受麻醉。此队列中包括该病所有变种。大多数患者有皮肤潮红,瘙痒,胃食管反流症和腹痛病史,一名患者有自发性过敏反应病史。不考虑该病的复杂性采用常规麻醉技术,整个围术期经过并不复杂,且无严重不良事件。

结论:回顾儿童肥大细胞增多症的主要特点和它所涉及的麻醉及围术期问题,并叙述此类儿科患者麻醉管理的实用方法。尽管很多麻醉中常规使用的药物据报道可引起肥大细胞脱颗粒,但并无依据证实与常规麻醉技术的差异是有必要的。然而为处理可能发生的不良事件,建议应了解此病所涉及的麻醉问题并仔细准备。

(黄凝译  薛张纲校)

BACKGROUND: Pediatric mastocytosis consists of a spectrum of clinical variants characterized by increased numbers of resident mast cells in various organ systems. Mast cells are instrumental in mediating anaphylaxis and patients with mastocytosis are at risk to develop provoked and unprovoked episodes of anaphylaxis.

METHODS: We examined perianesthetic records of patients with pediatric mastocytosis who were anesthetized for diagnostic and surgical procedures from 1993 to 2006. In addition, we conducted a literature review of the anesthetic experience in pediatric mastocytosis.

RESULTS: Twenty-two patients with pediatric mastocytosis, with a median age of 3.2 yr (range, 6 mo-20 yr) at the time of the procedure, were anesthetized for 29 diagnostic and surgical procedures. All variants of the disease are represented in this series. Most patients had a history of flushing, pruritus, gastro-esophageal reflux diseases, and abdominal pain; one patient had a history of spontaneous anaphylaxis. Routine anesthetic techniques were used and, despite the complexity of the disease, the perioperative courses were uncomplicated and without serious adverse events.

CONCLUSIONS: We reviewed the main features of pediatric mastocytosis, its anesthetic and perioperative implications, and describe a practical approach to the anesthetic management of pediatric patients with the disease. Although many drugs used routinely in anesthesia reportedly caused mast cell degranulation, deviations from routine anesthesia techniques are not necessarily warranted. However, an understanding of the anesthetic implications of the disease and meticulous preparation to treat possible adverse events are advised.

 

 

当前止吐方案对高危病人影响的前瞻性研究

The Impact of Current Antiemetic Practices on Patient Outcomes: A Prospective Study on High-Risk Patients
Paul F. White, Jerome F. O'Hara, Charles R. Roberson, Ronald H. Wender, Keith A. Candiotti, and The POST-OP Study Group

From the Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, Texas

Anesth Analg 2008 107: 452-458.

 

背景:该前瞻性、多中心、观察研究中将评价高危病人术后恶心呕吐(PONV)的发生率和持续时间,分析预防性和补救性止吐药物的使用,总结止吐药物使用指南对人群的有效性,其指南包括美国麻醉医师协会(ASA)和美国围麻醉期护理学会(ASPAN)指南。

方法:拟择期行腹腔镜手术或整形外科大手术的入选病人有下列两个或两个以上下列PONV危险因素:女性、PONV病史或运动晕动病、不吸烟。手术后第一个72h记录下列指标:止吐药物使用、呕吐事件发生、恶心严重性和因PONV对正常功能的干扰。止吐完全有效(CR)为无呕吐发生或无补救药物使用,止吐完全控制为CR和无中-重度恶心。分析受试者的ASA和ASPAN指南药物使用依从性对PONV发生率的影响。

结果:研究者中18%-40%病人有术后呕吐发生,其发生比例取决于使用止吐药物的数量。补救药物使用率为45%,其比例接近于先前报道的中-重度恶心发生率(47%)。因呕吐症状对生理功能干扰发生率为44%。使用3种及以上止吐药物产生的总体止吐效果优于使用少于1种预防性药物者。尽管受试者遵守ASA 和ASPAN使用指南,但CR率小于70%(ASA: 69%; ASPAN: 63%)。PONV完全控制率为10%低于3天研究期间CR率。

结论:对PONV高危因素病人,预防性使用3种或3种以上止吐药物对手术后病人72h内呕吐发生能产生积极结果。尽管遵从各个学会推荐的PONV使用指南,高危病人术后呕吐症状及其对病人正常活动干扰发生率仍大于30%。

(蒋宗明译 薛张纲校)

BACKGROUND: In this prospective, multicenter, observational study, we evaluated the incidence and time course of postoperative nausea and vomiting (PONV), assessed prophylactic and rescue antiemetic use in high-risk patients, and determined population-based effectiveness of antiemetics, including the impact of American Society of Anesthesiologists (ASA) and American Society of Perianesthesia Nurses (ASPAN) guideline compliance.

METHODS: Eligible patients undergoing elective laparoscopic or major plastic surgery possessed two or more of the following Apfel PONV risk factors: female gender, history of PONV or motion sickness, and nonsmoking status. Antiemetic use, emetic episodes, severity of nausea, and functional interference due to PONV were documented during the first 72 h after surgery. Complete response (CR) was defined as no emesis or rescue medication use, and complete control was defined as CR and no moderate-severe nausea. The effect of compliance (versus noncompliance) with ASA and ASPAN guidelines on PONV outcomes was also analyzed.

RESULTS: The proportion of patients experiencing postoperative emesis ranged from 18% to 40% depending on the number of antiemetics administered. The rate of rescue medication (45%) was similar to the reported incidences of moderate-to-severe nausea (47%) and functional interference due to emetic symptoms (44%). The administration of three or more antiemetics produced better patient outcomes overall compared to <1 prophylactic antiemetic. CR rates were <70% despite adherence to current organizational PONV management guidelines (ASA: 69%; ASPAN: 63%). The complete control rates were 10% lower than CR rates over the 3 day study period.

CONCLUSIONS: Administration of three or more prophylactic antiemetics had the most positive impact on emetic outcomes over 72 hrs in patients at risk of developing PONV. Although compliance with organizational PONV management guidelines improved patient outcomes, postoperative emetic symptoms and interference with patient functioning still occurred in more than 30% of these high-risk patients.

 

 

联合吸入性麻醉药之间对小鼠的最低肺泡浓度并不起到协同作用

Inhaled Anesthetics Do Not Combine to Produce Synergistic Effects Regarding Minimum Alveolar Anesthetic Concentration in Rats

Edmond I. Eger, II, Michael Tang, Mark Liao, Michael J. Laster, Ken Solt, Pamela Flood, Andrew Jenkins, Douglas Raines, Jan F. Hendrickx, Steven L. Shafer, Tanifuji Yasumasa, and James M. Sonner

From the *Department of Anesthesia and Perioperative Care, University of California, San Francisco, California; {dagger}Department of Anesthesia and Critical Care, Massachusetts General Hospital, and {ddagger}Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts; §Department of Anesthesiology, Columbia University, New York City, New York; ||Department of Anesthesiology, Emory University, Atlanta, Georgia; ¶Department of Anesthesia, Stanford University, Stanford, California; **Department of Biopharmaceutical Science, UCSF, San Francisco, California; and {dagger}{dagger}Department of Anesthesiology, Jekei University School of Medicine, Tokyo, Japan.

Anesth Analg 2008 107: 479-485.

 

背景:我们假设有歧异效价[指一种对最低肺泡浓度(MAC)的作用小,而另一种作用大]的两种吸入性麻醉药对某一受体或通道可能有着协同作用。并且,这种可加性的偏差对我们关于麻醉药物是在多位点来发挥麻醉效应的观点也起到了支持作用。

方法:相应的,我们研究了11对有着歧异效价(一种对MAC的作用小,一种作用大)的麻醉药物作用于某特一受体或通道时其MAC的可加性。所谓的“歧异作用”,我们通常是指在MAC上,那种对体内某特一受体或通道作用强的麻醉药其激动或阻断效应至少是较弱的那种的两倍(而通常是更多)。这些受体或通道包括:TREK-1/TASK-3钾通道、A型{gamma}-氨基丁酸受体、甘氨酸受体、N-甲基右旋天冬氨酸受体和乙酰胆碱受体。我们还研究了苯环丙烷的可加性,因为N-甲基右旋天冬氨酸的阻断剂MK-801对于这些麻醉药物的MAC值也有歧异效应。此外,我们还研究了包括笑气在内的四组吸入性麻醉药的配对,因为有文献报道当笑气与异氟醚合用时有次相加性(拮抗作用)的产生。

结果:除了有次相加性的笑气和异氟醚间的组合之外,其他所有的配对都得到了一个根据可加性得出的其预计值10%以内的结果。

结论:有观点认为,当遭遇有害刺激时,吸入性麻醉药是通过作用于某单一位点来达到麻醉制动效果的,而我们的结果正也与这一观点相一致。

(刘沁译 薛张纲校)

BACKGROUND: We hypothesized that pairs of inhaled anesthetics having divergent potencies [one acting weakly at minimum alveolar anesthetic concentration (MAC); one acting strongly at MAC] on specific receptors/channels might act synergistically, and that such deviations from additivity would support the notion that anesthetics act on multiple sites to produce anesthesia.

METHODS: Accordingly, we studied the additivity of MAC for 11 anesthetic pairs divergently (one weakly, one strongly) affecting a specific receptor/channel at MAC. By "divergently," we usually meant that at MAC the more strongly acting anesthetic enhanced or blocked the in vitro receptor or channel at least twice (and usually more) as much as did the weakly acting anesthetic. The receptors/channels included: TREK-1 and TASK-3 potassium channels; and {gamma}-aminobutyric acid type A, glycine, N-methyl-d-aspartic acid, and acetylcholine receptors. We also studied the additivity of cyclopropane-benzene because the N-methyl-d-aspartic acid blocker MK-801 had divergent effects on the MACs of these anesthetics. We also studied four pairs that included nitrous oxide because nitrous oxide had been reported to produce infraadditivity (antagonism) when combined with isoflurane.

RESULTS: All combinations produced a result within 10% of that which would be predicted by additivity except for the combination of isoflurane with nitrous oxide where infraadditivity was found.

CONCLUSIONS: Such results are consistent with the notion that inhaled anesthetics act on a single site to produce immobility in the face of noxious stimulation.

 

 

麻醉药相互协同作用:一项对麻醉机连接的理论分析

Additivity Versus Synergy: A Theoretical Analysis of Implications for Anesthetic Mechanisms

Steven L. Shafer, MD*{dagger}{ddagger}, Jan F. A. Hendrickx, MD, PhD{dagger}, Pamela Flood, MD*, James Sonner, MD§, and Edmond I. Eger, II, MD§

From the *Department of Anesthesiology, Columbia University, New York, New York; {dagger}Department of Anesthesia, Stanford University, Stanford, California; {ddagger}Departments of Biopharmaceutical Sciences and §Anesthesia and Perioperative Care, University of California at San Francisco, San Francisco, California; and ¶Department of Anesthesiology and Critical Care Medicine, OLV Hospital, Aalst, Belgium.

Anesth Analg 2008 107: 507-524.

 

背景:吸入性麻醉药假定作用于多种受体,在各方适度作用的叠加下产生固定的有害刺激。最近实验研究结果有了吸入性麻醉药相互影响的新发现。协同意味多方面的作用。这次尝试,我们探究相反的:在一方面有无叠加作用?

方法:用大量的聚集反应方法探索一对同一受体结合位置的竞争配体。构建一个电路来研究药物力量和不合理的浓度反映关系在有抑制物管理的连续电路中怎样被放大,在平行电路中被增强。集合的抑制物和增强电路进入信号处理单元来研究信号处理单位强制施加的影响所产生的附加交互作用。最后,协同,叠加,和占有部分受体之间的关系被探究来理解叠加后强制施加的影响。

结果:竞争性结合同一受体的药物与有相似效应的受体必须一一被添加。受体被抑制物固定在连续的电路中。在平行电路中被扩大,增加显著的药物力量与不合理的浓度反映关系。当集合的抑制物和增强的电路被安排进信号处理单元,相互作用会叠加或协同。关键在于药物浓度与影响效应和浓度与50%受体占有之间的关系,kd效应被低的浓度调节更可能被叠加。相似的,如果麻醉药效应出现在浓度在或超过50%受体被占有时,吸入性麻醉药在分离的地点作用不会显示叠加的交互作用。然而,如果麻醉药物效应出现在浓度非常低的受体被占有时,叠加作用会在其他麻醉作用受体上出现。

结论:药物在不同受体上的叠加作用只有在浓度依赖性药物浓度低于50%受体被占有时产生。

(刘婷洁译 薛张纲校)

BACKGROUND: Inhaled anesthetics have been postulated to act at multiple receptors, with modest action at each site summing to produce immobility to noxious stimulation. Recent experimental results affirm prior findings that inhaled anesthetics interact additively. Synergy implies multiple sites of action by definition. In this essay, we explore the converse: does additivity imply a single site of action?

METHODS: The interaction of one versus two ligands competing for the same binding site at a receptor was explored using the law of mass action. Circuits were then constructed to investigate how the potency of drugs and the steepness of the concentration versus response relationship is amplified by the arrangement of suppressors into serial circuits, and enhancers into parallel circuits. Assemblies of suppressor and enhancer circuits into signal processing units were then explored to investigate the constraints signal processing units impose on additive interactions. Lastly, the relationship between synergy, additivity, and fractional receptor occupancy was explored to understand the constraints imposed by additivity.

RESULTS: Drugs that compete for a single receptor, and that similarly affect the receptor, must be additive in their effects. Receptors that bind suppressors in serial circuits, or enhancers in parallel circuits, increase the apparent potency of the drugs and the steepness of the concentration versus response relationship. When assemblies of suppressor and enhancer circuits are arranged into signal processing units, the interactions may be additive or synergistic. The primary determinant is the relationship between the concentration of drug associated with the effect of interest and the concentration associated with 50% receptor occupancy, kd. Effects mediated by very low concentrations are more likely to be additive. Similarly, inhaled anesthetics that act at separate sites are unlikely to exhibit additive interactions if anesthetic drug effect occurs at concentrations at or above 50% receptor occupancy. However, if anesthetic drug effect occurs at very low levels of receptor occupancy, then additivity is expected even among anesthetics acting on different receptors.

CONCLUSIONS: Additivity among drugs acting on different receptors is only likely if the concentrations responsible for the drug effect of interest are well below the concentration associated with 50% receptor occupancy.

 

 

使用神经导航仪时六种脉搏氧饱和度仪的表现

The Performance of Six Pulse Oximeters in the Environment of Neuronavigation

Alexander M. Mathes, Sascha Kreuer, Sven O. Schneider, Stephan Ziegeler, Ulrich Grundmann From the Department of Anesthesiology, Critical Care and Pain Medicine, Saarland University Hospital, Homburg (Saar), Germany.

Anesth Analg 2008;107:541–4

 

背景:脉搏氧饱和度仪的使用已被公认是麻醉过程中的基本监护之一。然而,这种监护设备也很容易被多种外界干扰所影响。最近有看法指出,神经导航设备会影响脉搏氧饱和度仪的精确性。本次研究中,我们评估六种不同的脉搏氧饱和度仪在受到一种神经外科影像导航仪影响时的表现。另还将评估两种简单的屏蔽措施的效果。

方法:本研究入选二十个健康、成年、不抽烟的志愿者,在他们双手手指上夹上六种不同的脉搏氧饱和度仪,评估其心率、动脉氧饱和度、信号质量的基线。开启Brain Lab Vector Vision 神经导航系统仪后,记录下其对信号质量、饱和度识别的影响。并使用两种不同的屏蔽方法:棉毯及铝箔,分别重复测定记录值。

结果:影像导航仪的启动对信号质量及饱和度识别检测带来了有统计学意义的干扰。而这种干扰可在一定程度上被两种屏蔽方法所逆转。六种不同品牌的脉搏氧饱和度仪的信号质量有统计学意义的差别(p<0.001);氧饱和度识别也有统计学意义的差别(p<0.001);对于屏蔽方法的反应性也有统计学意义的差别(p<0.001)。由铝箔屏蔽的测试中,所有受试的探头监测到的饱和度值几乎没有受到影响。

结论:神经导航仪的红外线脉冲会影响到脉搏氧饱和度仪的监测。而将探头用铝箔屏蔽能显著地消除这种干扰。

(秦敏菊译 薛张纲校)

BACKGROUND: Although the use of pulse oximeters may be regarded a standard of care for monitoring anesthesia procedures, these monitors may be susceptible to various kinds of disturbances. Recently, it was suggested that neuronavigation equipment may interfere with pulse oximeter accuracy. In this study, we evaluated the effect of a neurosurgical image guidance system on the performance of six different pulse oximeters. Two simple shielding methods were evaluated.

METHODS: Twenty healthy, adult, nonsmoking volunteers were equipped with six different pulse oximeters on both hands. Baseline values for heart rate, arterial oxygen saturation, and signal quality were assessed. After activation of the Brain Lab VectorVision Neuronavigation System, the effects on signal quality and saturation recognition were evaluated. Measurements were repeated using two different shielding techniques, a cotton blanket and aluminum sheets.

RESULTS: Activation of the image guidance system resulted in a significant disturbance of signal quality and saturation detection, which was partially reversible by both shielding techniques. Significant differences were noted among the six brands of pulse oximeters for signal quality (P 〈0.001) and saturation recognition (P 〈0.001), and for the response to shielding methods (P〈0.001).Coverage of the probes with aluminum foil resulted an in undisturbed saturation recognition in all subjects with almost all monitors.

CONCLUSIONS: Infrared pulse waves from neurosurgical navigation equipment may interfere with pulse oximeter measurements. Shielding the probe with aluminum foil sufficiently eliminated the infrared interference.

 

 

冠状动脉支架:II 围手术期思考与处理

Coronary Artery Stents: II. Perioperative Considerations and Management

Lisa T. Newsome, MD, DMD*, Robert S. Weller, MD*, J. C. Gerancher, MD*, Michael A. Kutcher, MD*, and Roger L. Royster, MD*

From the Departments of *Anesthesiology and {dagger}Cardiology (Interventional Cardiology), Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Anesth Analg 2008; 107:570-590

 

装有冠状动脉支架的患者的围手术期管理,是临床医生所需面对的关系到患者生命安全的要点之一。无论是裸金属还是药物洗脱支架,围手术期支架血栓都是危及患者生命的严重并发症。非心脏手术似乎增加支架血栓、心肌梗死及死亡风险,特别是支架植入术后早期即接受手术的患者。术前停止双抗血小板治疗将进一步增加并发症发生可能。通常认为,除外出血风险显著大于继续的抗凝治疗,阿司匹林应在整个围手术期持续使用。我们建议局麻,因为术后是围手术期支架血栓发生可能最大的阶段。一旦发生支架血栓,24小时内患者应被送入心脏介入室,立即经皮冠状动脉介入治疗是治疗围手术期支架血栓的有效疗法。本文最后提出了围手术期裸金属及药物洗脱支架植入患者的不同处理建议。

(施颖译 薛张纲校)

The management of patients with coronary artery stents during the perioperative period is one of the most important patient safety issues clinicians confront. Perioperative stent thrombosis is a life-threatening complication for patients with either bare-metal or drug-eluting stents. Noncardiac surgery appears to increase the risk of stent thrombosis, myocardial infarction, and death, particularly when patients undergo surgery early after stent implantation. The incidence of complications is further increased when dual-antiplatelet therapy is discontinued preoperatively. It is generally agreed that aspirin must be continued throughout the perioperative period, except in circumstances when the risk of bleeding significantly outweighs the benefit of continued anticoagulation, such as procedures performed in a closed space. We present considerations for regional anesthesia, as well as postoperative recommendations as the occurrence of perioperative stent thrombosis appears to be greatest during this period. Immediate percutaneous coronary intervention is the definitive treatment for perioperative stent thrombosis, and 24-h access to an interventional cardiology suite should be readily available. Algorithms for perioperative management of patients with bare-metal and drug-eluting stents are proposed.

 

 

心脏手术后无创通气结合肺复张疗法的肺部效应

Pulmonary Effects of Noninvasive Ventilation Combined with the Recruitment Maneuver After Cardiac Surgery

Serdar Celebi, Özge Köner, Ferdi Menda, Oguz Omay, Ilhan Günay, Kaya Suzer, and Nahit Cakar

From the *Department of Anesthesiology and Intensive Care, Bakent University; Department of Anesthesiology and Intensive Care, Yeditepe University Hospital; Department of Cardiovascular Surgery, Bakent University; Department of Cardiovascular Surgery, Cardiology Institute, Istanbul University; and ||Department of Anesthesiology and Intensive Care, Istanbul University, Istanbul, Turkey.

Anesth Analg 2008; 107:614-619

 

背景:该研究的目标是评估开放性心脏手术后无创通气(NIV)结合或不结合肺复张疗法(RM)的肺效应。

方法 :100名冠脉旁路术后的病人被随机分为4组。1)术后机械通气结合持续膨肺的RM (RM 组, n = 25) 2)手术结束拔管后第一天里无创通气每6小时给与半小时的RM (RM-NIV 组, n = 25) 3)拔管后NIV (NIV 组, n = 25) 4)控制组,由不接受NIV和RM的病人组成(控制组, n = 25)。各组间比较肺功能测试,氧指数,和胸片下的肺膨胀不全的情况。

结果:机械通气期间的RM和拔管后的RM比其他干涉提供了更高的脉氧饱和度。RM-NIV 和NIV组在研究最后的氧饱和度比控制组好。控制组术后肺膨胀不全评分(均数: 1)比 RM组高(1; P = 0.03), 比RM-NIV高 (0; P < 0.01),比NIV组高 (0; P < 0.01)。NIV组在术后第二天的肺功能比其他组好,而术后第七天这一结果在各组之间差不多。

结论:NIV结合RM在机械通气期间和之后都提供更高的氧饱和度。NIV或结合RM的. NIV 比控制组提供更低的肺膨胀不全评分和更好的早期肺功能测试结果,而是否在机械通气期间,是否在加护病房和住院天数对此没有显著影响。心脏手术后采用NIV结合RM疗法有助于预防肺膨胀不全和低氧血症。

(孙鹏飞译 薛张纲校)

BACKGROUND: The aim of our study was to evaluate the pulmonary effects of noninvasive ventilation (NIV) with or without recruitment maneuver (RM) after open heart surgery.

METHODS: One-hundred patients undergoing coronary artery bypass surgery were randomized into four groups after the operation: 1) RM with sustained inflation during mechanical ventilation postoperatively (RM group, n = 25); 2) RM combined with NIV applied for 1/2-h periods every 6 h in the first postoperative day after tracheal extubation (RM-NIV group, n = 25); 3) NIV after tracheal extubation (NIV group, n = 25); and 4) a control group consisting of patients receiving neither RM nor NIV (control group, n = 25). Pulmonary function tests, oxygenation index, and atelectasis on chest radiograph were evaluated and compared among the groups.

RESULTS: RM provided higher arterial oxygen levels during mechanical ventilation and after tracheal extubation compared to other interventions. Oxygenation was better in the RM-NIV and NIV groups than in the control group (P = 0.02 and P = 0.008, respectively) at the end of the study. The postoperative atelectasis score of the control group (median: 1) was higher than those of the RM (1; P = 0.03), RM-NIV (0; P < 0.01) and NIV (0; P < 0.01) groups. Pulmonary function of the NIV groups on postoperative day 2 was better than in the other groups, whereas the tests were similar among the groups on postoperative day 7.

CONCLUSIONS: NIV associated with RM provided better oxygenation both during and after the mechanical ventilation period. NIV either alone or in combination with RM provided lower atelectasis scores and better early pulmonary function tests compared to the control group, without a significant difference regarding the duration of mechanical ventilation, intensive care unit stay, and the length of hospitalization. NIV combined with RM is recommended after open heart surgery to prevent postoperative atelectasis and hypoxemia.

 

 

关于在区域麻醉下接受颈动脉内膜剥脱术患者认知功能障碍的研究

A Study of Cognitive Dysfunction in Patients Having Carotid Endarterectomy Performed with Regional Anesthesia

Eric J. Heyer, MD, PhD, Mark I. Gold, MD, E. Will Kirby, BA, Joseph Zurica, BA, Elizabeth Mitchell, BA, Hadi J. Halazun, BA, Lauren Teverbaugh, BA, Robert R. Sciacca, EngScD, Robert A. Solomon, MD, Donald O. Quest, MD, Thomas S. Maldonado, MD, Thomas S. Riles, MD, and E. Sander Connolly, Jr, MD

Anesth Analg 2008 107: 636-642.

 

背景:既往研究发现,与对照组相比,在全身麻醉下接受颈动脉内膜剥脱术(CEA)的患者中约25%在术后1天到一个月内发生认知功能障碍。在本次研究中,我们假定,与接受镇静治疗的对照组相比,在区域麻醉下接受CEA术的患者会在术后1天出现认知功能障碍。

方法:为验证假设,我们招收60名患者加入前瞻性研究。在区域麻醉下行CEA术的41位患者接受颈深丛及浅丛神经阻滞。对照组由19位在镇静治疗下接受冠状动脉造影术或支架术的患者组成。为解决重复进行认知水平测验而引起的“练习效果”问题,对照组是必不可少的。实验组患者来源于纽约医学研究中心,对照组患者来源于哥伦比亚长老会医学研究中心。所有患者的认知水平经由一系列既经证实有效的神经心理学测验评估。术后一天与术前相比的差异性表现由事件发生率和群组发生率来评价。

结果:术后一天,在区域麻醉下接受CEA术的患者中有24.4% 发生显著的认知功能障碍,此处的“显著”定义为比对照组的平均评分低两个标准差以上。

结论:在区域麻醉下接受CEA术的患者有发生术后认知功能障碍的可能,其几率与以往报导过的全麻下CEA术者没有明显差别。

(夏俊明译 薛张纲校)
METHODS: To test this hypothesis, we enrolled 60 patients in a prospective study. CEA regional was performed with superficial and deep cervical plexus blocks in 41 patients. The control group consisted of 19 patients having coronary angiography or coronary artery stenting performed with sedation. A control group is necessary to account for the "practice effect" associated with repeated cognitive testing. The patients from the CEA regional group were enrolled at New York Medical Center and the control group at Columbia-Presbyterian Medical Center. The cognitive performance of all patients was evaluated using a previously validated battery of neuropsychometric tests. Differences in performance, 1 day after compared with before surgery, were evaluated by both event-rate and group-rate analyses.

BACKGROUND: In previous studies, we found that approximately 25% of patients having carotid endarterectomy with general anesthesia (CEA general) develop cognitive dysfunction compared with a surgical control Group 1 day and 1 mo after surgery. In this study, we tested the hypothesis that patients having CEA with regional anesthesia (CEA regional) will develop significant cognitive dysfunction 1 day after surgery compared with a control group of patients receiving sedation 1 day after surgery. We did not study persistence of dysfunction.

RESULTS: On postoperative day 1, 24.4% of patients undergoing CEA regional had significant cognitive dysfunction, where "significant" was defined as a total deficit score ≥2 SD worse than the mean performance in the control group.

CONCLUSIONS: Patients undergoing CEA regional had an incidence of cognitive dysfunction which was not different than patients having CEA general as previously published and compared with a contemporaneously enrolled group.

                                                          

 

使用帕瑞考昔钠20mg一天两次的多日用药法能减轻全髋置换术后的疼痛

A Multiple-Day Regimen of Parecoxib Sodium 20 mg Twice Daily Provides Pain Relief After Total Hip Arthroplasty

Viscusi, Eugene R. MD; Gimbel, Joseph S. MD; Halder, Andreas M. MD, PhD; Snabes, Michael MD, PhD; Brown, Mark T. MD; Verburg, Kenneth M. PhD

Michael Snabes is currently at MCS Medical Consulting, Winnetka, Illinois

From the *Department of Anesthesiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania; {dagger}Arizona Research Center, Phoenix, Arizona; {ddagger}Klinik für Endoprothetik, Waldhausstrasse, Sommerfeld, Germany; §Pfizer Global Research and Development, Skokie, Illinois; and ||Pfizer Global Research and Development, New London, Connecticut.

Anesth Analg 2008 107: 652-660.

 

背景:这项多中心、多种剂量、随机、双盲、平行分组的研究比较了在全髋置换术后使用帕瑞考昔钠(帕瑞考昔)的两种给药方案对照安慰剂组的止痛效果和安全性。

方法:在第一试验日,490名患者在术后得到静脉注射帕瑞考昔40mg的起始负荷剂量,随后对490名患者中的484名再次使用帕瑞考昔20mg。第二试验日随机挑选479名患者进行双盲治疗:帕瑞考昔20mg bid组(n=159),使用安慰剂后使用帕瑞考昔20mg qd组(n=159)和安慰剂组(n=161)。

结果:帕瑞考昔20mg bid治疗组的病人在第2到5天比安慰剂组病人显示明显低的24小时总疼痛强度(SPI-24)评分和改善的病人的药物治疗研究的全球评价(PGESM)等级(P<0.05)。帕瑞考昔20mg qd治疗组的病人在第3、4天的SPI-24评分比安慰剂组显著的低P<0.05)PGESM评级在第5天比安慰剂组改善。除了发热、呕吐和注意力不集中在安慰剂组中较其他帕瑞考昔治疗组更为常见(P<0.05),不良事件的发生率在所有治疗组中相似。

结论:帕瑞考昔20mg一天一次或两次的多日给药法在全髋置换术后是有效和普遍耐受的。

(宣丽真译 薛张纲校)

BACKGROUND: This multicenter, multiple-dose, randomized, double-blind, parallel-group study compared the analgesic efficacy and safety of two dosing regimens of parecoxib sodium (parecoxib) versus placebo after total hip arthroplasty.

METHODS: On study Day 1, 490 patients received a postoperative initial loading dose of IV parecoxib 40 mg, followed by a re-dose of parecoxib 20 mg in 484 of 490 patients. Subsequently, 479 randomized patients received double-blind treatment with parecoxib 20 mg bid (n = 159), parecoxib 20 mg qd (n = 159) followed by placebo, or placebo (n = 161) on Day 2.

RESULTS: Patients treated with parecoxib 20 mg bid reported significantly lower summed pain intensity over 24 h (SPI-24) scores and improved patients’ global evaluation of study medication (PGESM) ratings compared with placebo-treated patients on Days 2 to 5 (P < 0.05). For patients treated with parecoxib 20 mg qd, SPI-24 scores were significantly lower on Days 3 and 4 (P < 0.05), and PGESM ratings significantly improved on Day 5 compared with placebo. The incidence of adverse events was similar in all treatment groups with the exception of fever, vomiting and impaired concentration, which were significantly more common in the placebo group compared with one or other of the parecoxib treatment groups (P < 0.05).

CONCLUSION: Multiple-day administration of parecoxib 20 mg once or twice daily is effective and generally well tolerated after total hip arthroplasty.

 

 

咪达唑仑在关节镜膝盖手术以后镇痛的剂量-效果研究

A Dose-Ranging Study of Intraarticular Midazolam for Pain Relief After Knee Arthroscopy

Yatindra Kumar Batra, MD, MNAMS, FAMS*, Rajesh Mahajan, MD*, Sushil Kumar, MD*, Subramanyam Rajeev, MD, DNB*, and Mandeep Singh Dhillon, MS

From the Departments of *Anaesthesia and Intensive Care and {dagger}Orthopaedic Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India.

Anesth Analg 2008 107: 669-672.

 

背景: 各种各样的镇痛药技术被用于在关节镜膝盖手术以后处理手术后痛苦。 关节腔内使用咪达唑仑的镇痛作用和中枢神经内使用咪达唑仑的镇痛作用相似。

方法: 对60名ASA I或II级的接受关节镜检查的患者实行全身麻醉,并随机化接受关节腔内注射咪达唑仑50 µg/kg,75 µg/kg或者等渗盐。我们通过以下几个方面评估镇痛药的效果:直观镇痛评分、首次要求镇痛的时间、累计镇痛药的消耗。患者总共观察48 h。

结果:相比于等渗盐,早期关节腔内注射咪达唑仑可以明显降低直观镇痛评分。两药量都可以延长首次要求镇痛的时间(4.7 和4.6 vs 0.7 h)使用两种剂量的药物对于累计镇痛药的消耗方面没有统计学的差异。

结论: 我们认为,在关节镜手术后,相比于安慰剂,关节腔内注射咪达唑仑可以减轻术后疼痛, 然而这种镇痛作用镇痛是相对短期的。

(章一静译 薛张纲校)

BACKGROUND: A variety of analgesic techniques have been used to manage postoperative pain after arthroscopic knee surgery. Intraarticular midazolam may have an analgesic effect similar to that seen when midazolam is used in a centroneuraxial fashion.

METHODS: Sixty ASA status I or II patients undergoing knee arthroscopy with general anesthesia were randomized to receive intraarticular midazolam 50 µg/kg, 75 µg/kg, or isotonic saline. We assessed the efficacy of the analgesic technique with visual analog  scale pain scores, time until first request for analgesics, and cumulative analgesic consumption. Patients were observed for 48 h.

RESULTS: The addition of intraarticular midazolam significantly reduced visual analog pain scores in the early postoperative period compared with saline. Both doses similarly prolonged duration until first request for analgesic compared with saline (4.7 and 4.6 vs 0.7 h). There was no statistically significant difference between the two doses of midazolam or cumulative 48 h analgesic consumption.

CONCLUSIONS: We conclude that when intraarticular midazolam was compared with placebo there was a reduction in pain after day-case arthroscopic knee surgery; however, this pain relief was of relatively short duration

 

 

鞘内注射可乐定可以抑制小鼠脊髓背侧脚神经元的N-甲基-D-天门冬氨酸受体NR1磷酸化引起的神经性疼痛

Intrathecal Clonidine Suppresses Phosphorylation of the N-Methyl-D-Aspartate Receptor NR1 Subunit in Spinal Dorsal Horn Neurons of Rats with Neuropathic Pain

Dae-Hyun Roh, DVM, MS*, Hyun-Woo Kim, DVM, PhD{dagger}, Seo-Yeon Yoon, DVM, PhD*, Hyoung-Sig Seo, DVM, MS*, Young-Bae Kwon, DVM, PhD{ddagger}, Ho-Jae Han, DVM, PhD§, Alvin J. Beitz, PhD||, and Jang-Hern Lee, DVM, PhD*

From the *Department of Veterinary Physiology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea; {dagger}Department of Physiology, College of Medicine, Chungnam National University, Daejeon, South Korea; {ddagger}Department of Pharmacology, Institute for Medical Science, Chonbuk National University Medical School, Jeonju, South Korea; §Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University, Gwang-ju, South Korea; and ||Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN.

Anesth Analg 2008 107: 693-700.

 

背景:鞘内注射α受体拮抗剂可乐定有镇痛的效果。尽管有一些关于可乐定相关的镇痛机制假设,但是作为主要抗伤害性刺激机制的N-甲基-D-天门冬氨酸(NMDA)受体,其与可乐定作用的关系尚没有很多研究。我们设计了这个试验来研究可乐定或者其他镇痛药物是否可以影响小鼠脊髓NMDA受体,从而缓解慢性缩窄性损伤(CCI)引起的神经病症状。

方法:单侧CCI的小鼠分别鞘内注射可乐定(1,5,20ug/小鼠),[d- 丙氨酸2, N甲基烟酰胺-苯丙氨酸4, 甘氨酸-ol5]-脑啡肽 (DAMGO, µ 阿片受体拮抗剂, 1 µg/小鼠),加巴喷丁(抗惊厥药物,100 µg/小鼠)。注射之后,我们测定了小鼠对热或机械刺激的痛觉反应,并使用免疫组化评估脊髓磷酸化的NMDA受体亚单位1(pNR1)的表达。

结果:CCI手术后两周,小鼠表现出对热和机械刺激的异常痛觉敏感,脊髓背侧脚的pNR1神经元的表达也增加。鞘内注射可乐定(20 µg/小鼠),DAMGO和加巴喷丁可以潜在降低机械或热刺激引起的痛觉反应。重要的是,鞘内注射可乐定,但是不注射DAMGO和加巴喷丁,在注射后30min可以剂量依赖性的降低CCI导致的脊髓背侧脚的pNR1的表达。另外,可乐定可以抑制CCI导致的脊髓背侧角NR1磷酸化,但是在注射可乐定之前10min,鞘内注射α-2受体拮抗剂咪唑克生(40 µg/小鼠),可以完全逆转其对抗痛觉过敏的效果。

结论:我们的数据显示,鞘内注射可乐定的对抗痛觉过敏的作用与降低脊髓NMDA受体磷酸化有关,并提示可乐定的潜在的作用机制。

(陈珺珺译 薛张纲校)

BACKGROUND: Intrathecal (IT) administration of the {alpha}-2 adrenoceptor agonist, clonidine, produces significant analgesic effects. Although several mechanisms underlying clonidine-induced analgesia have been proposed, the possible interaction with N-methyl-D-aspartate (NMDA) receptors as a major antinociceptive mechanism has not been addressed. We designed the present study to determine whether clonidine or other analgesics can affect spinal NMDA receptor activation in rats with chronic constriction injury (CCI)-induced neuropathy.

METHODS: Rats underwent unilateral CCI, and received IT clonidine (1, 5, 20 µg/rat), [d-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO, µ opioid receptor agonist, 1 µg/rat), gabapentin (anticonvulsant, 100 µg/rat) or vehicle 2 wks later. After drug injection, we measured the pain response to thermal or mechanical stimuli and used immunohistochemistry to evaluate spinal cord phosphorylated NMDA-receptor subunit 1 (pNR1) expression.

RESULTS: Two weeks after CCI surgery, rats displayed significant mechanical allodynia and thermal hyperalgesia, and the spinal cord dorsal horn showed a significant increase in the number of pNR1 immunoreactive neurons. IT injection of clonidine (20 µg/rat), DAMGO and gabapentin potently reduced mechanical allodynia and thermal hyperalgesia. Importantly, IT clonidine, but not IT DAMGO or gabapentin, dose-dependently reduced CCI-induced pNR1 expression in all lamina of the spinal cord dorsal horn by 30 min after injection. In addition, IT injection of the {alpha}-2 adrenoceptor antagonist, idazoxan (40 µg/rat) 10 min before clonidine injection completely reversed clonidine’s anti hyperalgesic and anti allodynic effects, as well as clonidine’s suppressive effect on CCI-induced NR1 phosphorylation in the spinal cord dorsal horn.

CONCLUSIONS: Our data indicate that IT clonidine’s antihyperalgesic/antiallodynic effect on neuropathic pain is associated with a significant reduction in spinal NMDA receptor phosphorylation and suggests a potentially novel mechanism of clonidine’s action.

 

儿童心脏手术人群中抗肝素-血小板因子4抗体的形成的发病率和意义

The Incidence and Implications of Anti-Heparin-Platelet Factor 4 Antibody Formation in a Pediatric Cardiac Surgical Population

Mary P. Mullen, MD, PhD*{dagger}, David L. Wessel, MD*{dagger}, Kristen C. Thomas, MS, RN*, Kimberlee Gauvreau, ScD*§, Ellis J. Neufeld, MD, PhD*{dagger}, Francis X. McGowan, Jr, MD*{dagger}, and James A. DiNardo, MD*{dagger}

From the *Children's Hospital Boston and {dagger}Harvard Medical School, §Harvard School of Public Health, Boston, Massachusetts.

Anesth Analg 2008 107: 371-378.

 

背景:儿童心脏手术人群中血清抗肝素-血小板因子4抗体的发病率和意义仍未阐明。作者前瞻性研究以下两种群体中血清转化的发生率:首次施行心脏手术的新生儿以及有普通肝素使用史的再次心脏手术儿童。

方法:研究连续135名患者:新生儿组:60名新生儿,第一次心脏外科手术;再次手术组:75名,再次心脏手术者。分别对术前和术后5天及10天的血液样本进行酶联免疫吸附试验,从而确认是否有PF4免疫球蛋白GAM抗体。

结果:两组患者术前均未检测到抗肝素/抗肝素-血小板因子4抗体。在术后5天新生儿组1名患者(1.7%)检测到抗体;再次手术组12名患者(16%)检测到抗体;组间差异显著(P=0.006)。术后10天,新生儿组1名患者(1.7%)检测到抗体;再次手术组39名患者(52%)检测到抗体(P<0.001)。再次手术组的患者术后10天的血清与普通肝素使用史间有良好的相关性(P=0.003)。在任一新生儿组的患者中,未发现肝素诱导的血小板减少症(HIT)。再次手术组中一名患者(1.3%)发生了血清转化并发生了HIT,但没有发生血栓或者皮肤病损。

结论:HIT在儿童心脏手术患者中鲜有发生。在再次手术的儿童中,术后10天的抗肝素-血小板因子4抗体血清转化的发病率大约为50%,在成人心脏外科手术患者中有相似的发现。年龄和普通肝素使用史与此血清转化率有关。相反,新生儿初次手术组中血清转化率比较低。

(朱紫瑜 译 陈杰 校)

BACKGROUND: The incidence and implications of anti-heparin-platelet factor 4 (PF4) antibody seroconversion in the pediatric cardiac surgical population remain largely unexplored. We sought to prospectively characterize the incidence of seroconversion in two populations: neonates undergoing primary cardiac surgery and children undergoing reoperative cardiac surgery with a history of unfractionated heparin (UFH) exposure.

METHODS: One hundred and thirty-five consecutive patients were studied: Neonatal = 60 neonates, first time cardiac surgery. Reoperative (ReOp) = 75 children, reoperative cardiac surgery. Preoperative and postoperative day (POD) 5 and 10 blood samples were used to determine the presence of PF4 immunoglobulin (Ig)G, IgA, and IgM antibodies with enzyme-linked immunosorbent assay.

RESULTS: No anti-heparin/PF4 antibodies were detected preoperatively in either group. On POD 5, antibodies were present in 1 of 60 (1.7%) Neonatal; and in 12 of 75 (16%) ReOp; P = 0.006. On POD 10, antibodies were present in 1 of 60 (1.7%) Neonatal; and in 39 of 75 (52%) ReOp; P < 0.001. Seroconversion in ReOp patients on POD 10 was significantly associated (P = 0.03) with previous UFH exposures. Heparin-induced thrombocytopenia (HIT) was not diagnosed in any Neonatal patients. One ReOp patient (1.3%) seroconverted and developed HIT without thrombosis or skin lesions.

CONCLUSIONS: HIT is a rare occurrence in pediatric cardiac surgical patients. The incidence of anti-heparin-PF4 antibody seroconversion in children undergoing reoperation is approximately 50% at 10 days postoperatively, a finding similar to that reported in adult cardiac surgical patients. Both age and previous UFH exposure correlate with this rate of seroconversion. In contrast, the rate of seroconversion in neonates undergoing first time surgery is substantially lower.

 

小儿吸入麻醉诱导期间不良行为依从的预测因子

Factors Predictive of Poor Behavioral Compliance During Inhaled Induction in Children

Anna M. Varughese, MD, MPH*{dagger}, Todd G. Nick, PhD{dagger}{ddagger}, Joel Gunter, MD*{dagger}, Yu Wang, MS{ddagger}, and C. Dean Kurth, MD*{dagger}

From the *Department of Anesthesiology; {dagger}Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine; and {ddagger}Center for Epidemiology and Biostatistics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Anesth Analg 2008 107: 413-421.

 

背景:术前确定小儿吸入麻醉诱导期间有情绪痛苦及不良行为依从有助于进行定向干预以减少痛苦,从而改善麻醉质量。本文作者探索了识别患者、操作、健康护理系统等因素预测诱导期间不良行为依从的方法。

方法:选择861名发育正常的1-13岁,ASAI-III级,进行吸入麻醉诱导的小儿。所有的麻醉诱导在诱导室中由父母陪伴下完成。行为习惯通过ICC评估,即一种观察量表,测定诱导期间对行为进行观察所获得的数值,ICC≥4认为行为顺从性差。行为依从性通过一个多变量定向逻辑回归模型取得,多变量模型特征由c统计法评估。

结果21%小儿在麻醉诱导时出现不良行为依从。年龄小(<4y, p<0.001),术前准备时间短(p=0.004, 术前焦虑(修订的耶鲁术前焦虑标准>40p=0.016)等因素增加了不良行为依从可能性。先前的麻醉经历增加了学龄儿童的可能性(p=0.046);这种影响在参加术前培训的孩子中有所改善(p=0.018)。这些因素在有不良行为依从与良好的行为依从(ICC=0)(c统计=0.75)的孩子间有差异。

结论:不良行为依从的预测因子有年龄,先前的麻醉经历,以及在术前门诊进行的术前培训,术前准备时间及焦虑程度等。包含这些因子的预测程序,有助于分辨能从行为或药理干预受益的孩子以及不需要干预的低风险的孩子。

(潘钱玲 译 陈杰 校)

BACKGROUND: Preoperative identification of children at risk of emotional distress and poor behavioral compliance during inhaled induction of anesthesia allows targeted interventions to reduce distress, thereby enhancing the quality of the anesthetic experience. We sought to identify patient, procedural, and health care system factors predictive of poor behavioral compliance during induction.

METHODS: We studied 861 developmentally appropriate children ages 1–13 yr, The American Society of Anesthesiologists physical status I to III, presenting for inhaled induction of anesthesia. All inductions were performed in an induction room with parent(s) present. Behavioral compliance was assessed using the Induction Compliance Checklist (ICC), an observational scale consisting of 10 behaviors scored as the number of behaviors observed during induction; ICC ≥4 was considered poor behavioral compliance. A multivariable ordinal logistic regression model for behavioral compliance was generated and the performance of the multivariable model was evaluated by the c statistic.

RESULTS: Twenty-one percent of children exhibited poor behavioral compliance on induction. Factors increasing the odds of poor behavioral compliance were younger age (<4 yr, P < 0.0001), shorter preoperative preparation time (P = 0.004), and high anxiety levels in the preoperative clinic (modified-Yale preoperative anxiety scale >40; P = 0.016). Previous anesthesia experience increased the odds in school-age children (P = 0.046); this effect was ameliorated in children attending the preoperative tour (P = 0.018). The model using these factors demonstrated moderate discrimination between children with poor compliance and those with perfect compliance (ICC = 0) (c statistic = 0.75).

CONCLUSIONS: Factors predictive of poor behavioral compliance were age, previous anesthesia, preoperative tour attendance, preoperative preparation time and anxiety levels in the preoperative clinic. These factors, bundled into a predictive algorithm, may help identify children who could benefit from behavioral or pharmacological interventions and avoid use of interventions to those at low risk.

 

一项随机双盲研究:评估三种不同剂量的帕洛诺司琼与安慰剂对预防术后恶心呕吐的有效性与安全性

A Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Three Different Doses of Palonosetron Versus Placebo for Preventing Postoperative Nausea and Vomiting

Keith A. Candiotti, MD*, Anthony L. Kovac, MD{dagger}, Timothy I. Melson, MD{ddagger}, Giuseppina Clerici, MD§, Tong Joo Gan, MB, FRCA||, and The Palonosetron 04–06 Study Group

From the *Departments of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami, Miami, Florida; {dagger}Department of Anesthesiology, University of Kansas Medical Center, Kansas City, Kansas; {ddagger}Helen Keller Memorial Hospital, Sheffield, Alabama; §Research and Development Department, Helsinn Healthcare SA, Lugano, Switzerland; and ||Department of Anesthesiology, Duke University Medical Centre, Durham, North Carolina.

Anesth Analg 2008 107: 445-451.

 

背景:为了评估三种剂量的新型5-HT3受体阻滞剂---帕洛诺司琼的有效性及安全性,作者进行这一随机双盲研究,观察术后72小时的PONV(术后恶心呕吐)发病率及严重程度。

方法:作者对574名门诊腹部手术或腹腔镜下行妇科手术病人,根据其性别、有无PONV史、有无运动病、是否吸烟分层。有≥2PONV危险因素的病人入组并在麻醉诱导前即刻随机静脉予以三种剂量(0.025mg0.05mg0.075mg)帕洛诺司琼中一种或安慰剂。随后观察帕洛诺司琼的主要疗效指标(co-primary efficacy end-points)包括术后0-24小时、24-72小时两个时段的完全缓解率(指无呕吐及不需补救药物,CR)。

结果:部分病人在第一个24小时出现与帕洛诺司琼剂量相关的CR。而在术后0-24小时这一时段安慰剂及帕洛诺司琼(0.075mg)的CR率分别为26%43%P=0.004),在术后24-72小时,安慰剂及帕洛诺司琼(0.075mg)的CR率分别为41%49%P=0.188)。与安慰剂相比帕洛诺司琼(0.075mg可以显著降低严重恶心发生率(P=0.042)及减轻术后0-24小时内PONV对病人的影响(P=0.004)。

结论:帕洛诺司琼(0.075mg)能显著降低术后0-24小时内的CR率,减轻恶心程度,减少病人术后PONV的发生。

(陶颖莹 译 陈杰 校)

BACKGROUND: In this randomized, double-blind study we assessed the efficacy and safety of three different doses of the 5-HT3 receptor antagonist palonosetron, compared with placebo, on the incidence and severity of postoperative nausea and vomiting (PONV) for 72 h postsurgery.

METHODS: Five hundred seventy-four patients undergoing either outpatient abdominal or gynecological laparoscopic surgery were stratified according to gender, history of PONV or motion sickness, and nonsmoking status. Patients with ≥2 PONV risk factors were eligible and randomized to receive one of three doses of IV palonosetron (0.025 mg, 0.050 mg, or 0.075 mg) or placebo immediately prior to induction of anesthesia. Co-primary efficacy end-points included complete response (CR: no emetic episodes and no rescue medication) during the 0 to 24 h and 24 to 72 h postoperative time intervals.

RESULTS: A dose-response trend in the proportion of patients with a CR was observed with increasing doses of palonosetron in the first 24 hrs. CR rates for placebo and palonosetron 0.075 mg were 26% and 43%, respectively, for the 0 to 24 h postoperative interval (P = 0.004), and 41% and 49%, respectively, for the 24 to 72 h interval (P = 0.188). Compared with placebo, palonosetron 0.075 mg was associated with a significant downward shift toward less intense nausea (P = 0.042) and with significant reduction in the impact of PONV on patient functioning (P = 0.004) during the 0 to 24 h interval.

CONCLUSIONS: A single 0.075-mg IV dose of palonosetron significantly increased the CR rate (no emetic episodes and no rescue medication) from 0 to 24 h, decreased nausea severity and patients experienced significantly less interference in their postoperative function due to PONV.

 

帕诺斯琼在分子水平与5-羟色胺受体间独特的相互作用

Palonosetron Exhibits Unique Molecular Interactions with the 5-HT3 Receptor

Camilo Rojas, PhD*, Marigo Stathis, MS*, Ajit G. Thomas, MSE*, Edward B. Massuda, MS*, Jesse Alt, BS*, Jie Zhang, PhD*, Ed Rubenstein, MD{dagger}, Silvia Sebastiani, PhD{ddagger}, Sergio Cantoreggi, PhD§, Solomon H. Snyder, MD||, and Barbara Slusher, PhD*

From the *Research and Translational Development, MGI PHARMA INC, Baltimore, MD; {dagger}Medical & Scientific Affairs, MGI PHARMA INC, Bloomington, Minnesota; {ddagger}Medical Marketing, HELSINN HEALTHCARE SA, Lugano, Switzerland; §Research and Development, HELSINN HEALTHCARE SA, Lugano, Switzerland; and ||Department of Neuroscience, Johns Hopkins Medical School, Baltimore, Maryland.

Anesth Analg 2008 107:469-478

 

背景:在Ⅲ期临床试验中,与其它5-羟色胺受体拮抗剂相比,帕诺斯琼被证实能更有效地预防急性、迟发性,及其它由化疗所引发的恶心和呕吐。帕诺斯琼强大的临床效力可能部分源于它有更长的半衰期,及其与受体间更大的亲和力。然而,帕诺斯琼的这些特性并不足以解释它的药效。作者试图进一步阐明不同5-羟色胺受体间的差异,希望这有助于解释临床的观察结果。

方法:作者用3H-帕诺斯琼、3H-格拉琼斯和3H-奥坦西隆进行受体位点饱和结合试验,以获得相应的Scatchard分析和Hill系数。通过诊断性平衡结合试验和动力学解离试验,评价帕诺斯琼、格拉琼斯和奥坦西隆与5-羟色胺受体间的相互竞争和变构作用。最后,比较了三种拮抗剂对受体功能的长期效应,通过检测表达5-羟色胺受体的HEK293细胞内的钙内流实现的。

结果:通过ScatchardHill曲线分析结合等温线,作者发现单一双分子结合的格拉琼斯和奥坦西隆与帕诺斯琼之间存在协同效应。平衡诊断试验表明帕诺斯琼对3H配体有不同的结合效应,这说明帕诺斯琼是一种异构性拮抗剂,而格拉斯琼和奥坦西隆是竞争性拮抗剂。通过测定解离速率发现,帕诺斯琼是一种变构的效应物,它能够加快格拉斯琼和奥坦西隆与受体的解离速率。帕诺斯琼与5-羟色胺受体间不同的结合模式影响受体功能的发挥。在这些试验中,用每一种拮抗剂孵化细胞,然后使其无限稀释和解离2.5小时。可以观察到,在用格拉斯琼或奥坦西隆孵化的细胞中出现了与未暴露于5-羟色胺受体的对照组细胞中相似的钙离子内流;与其相反,在用帕诺斯琼孵化的细胞中观察到了强大的钙内流抑制效应。

结论:帕诺斯琼是一种异构性结合剂,当它与5-羟色胺受体结合时,产生协同效应。同时,帕诺斯琼触发的功能性效应的持续时间长于它与细胞表面受体的结合时间。它与受体的结合位点不同,及其导致的不同的受体功能可能与它独特的临床效益相关。作者认为,这是首次在分子水平探讨帕诺斯琼与5-羟色胺受体之间的相互作用,这也是它与其它5-羟色胺受体拮抗剂的截然不同之处。

(周姝婧 陈杰

BACKGROUND: Palonosetron is a 5-HT3-receptor antagonist (5-HT3-RA) that has been shown to be superior to other 5-HT3-RAs in phase III clinical trials for the prevention of acute, delayed, and overall chemotherapy-induced nausea and vomiting. The improved clinical efficacy of palonosetron may be due, in part, to its more potent binding and longer half-life. However, these attributes alone are not sufficient to explain the results with palonosetron. We sought to elucidate additional differences among 5-HT3-RAs that could help explain the observations in the clinic.

METHODS: Receptor site saturation binding experiments were performed with [3H] palonosetron, [3H] granisetron, and [3H] ondansetron to obtain the corresponding Scatchard analyses and Hill coefficients. Diagnostic equilibrium binding experiments and kinetic dissociation experiments were conducted to examine competitive versus potential allosteric interactions between ondansetron, granisetron and palonosetron and the 5-HT3 receptor. Finally, the long-term effect of the three antagonists on receptor function as measured by Ca2+ influx in HEK 293 cells expressing the 5-HT3-receptor was compared.

RESULTS: Analyses of binding isotherms using both Scatchard and Hill plots suggested positive cooperativity for palonosetron and simple bimolecular binding for both granisetron and ondansetron. Equilibrium diagnostic tests discriminated differential effects of palonosetron on [3H] ligand binding indicating that palonosetron was an allosteric antagonist whereas granisetron and ondansetron were competitive antagonists. Using dissociation rate strategies, palonosetron was shown to be an allosteric modifier that accelerated the rate of dissociation from the receptor of both granisetron and ondansetron. Differences in the binding mode of palonosetron to the 5-HT3 receptor were shown to have an impact on receptor function. In these experiments, cells were incubated with each antagonist, followed by infinite dilutions and dissociation for 2.5 h; cells previously incubated with either granisetron or ondansetron showed calcium-ion influx similar to control cells that had not been exposed to a 5-HT3 receptor antagonist. In contrast, substantial inhibition of calcium-ion influx was observed in cells that had been incubated with palonosetron.

CONCLUSIONS: Palonosetron exhibited allosteric binding and positive cooperativity when binding to the 5-HT3 receptor. Palonosetron also triggered functional effects that persisted beyond its binding to the 5-HT3 receptor at the cell surface. Differences in binding and effects on receptor function may be relevant to the unique beneficial actions of palonosetron. To our knowledge, this is the first report showing palonosetron's interaction with the 5-HT3 receptor at the molecular level, clearly differentiating it from other 5-HT3-RAs.

 

 协同作用是普遍规律?关于产生催眠和肢体活动消失的麻醉药相互作用的综述

Is Synergy the Rule? A Review of Anesthetic Interactions Producing Hypnosis and Immobility

Jan F. A. Hendrickx, MD, PhD*, Edmond I. Eger, II, MD{dagger}, James M. Sonner, MD{dagger}, and Steven L. Shafer, MD{ddagger}

From the *Department of Anesthesia, Stanford University School of Medicine, Stanford, California; {dagger}Department of Anesthesia and Perioperative Care, UCSF; and {ddagger}Department of Anesthesia, Stanford University School of Medicine, Stanford, CA, and Department of Biopharmaceutical Science, University of CA at San Francisco, San Francisco, California.

Anesth Analg 2008 107: 494-506.

 

背景:药物的相互作用可以揭示药物作用的机制:相加作用提示作用于同一位点,协同作用提示作用于不同位点。笔者应用这一推理回顾了已出版的最终会引起催眠和肢体活动消失的麻醉药物的相互作用。

方法:笔者搜索了Medline上所有的列有下列药物相互作用的原稿:丙泊酚、依托咪酯、美索比妥、硫苯妥钠、咪唑安定、地西泮、氯胺酮、右美托咪定,可乐定、吗啡、芬太尼、舒芬太尼、阿芬太尼、瑞芬太尼、氟哌利多、甲氧氯普胺、利多卡因、氟烷、恩氟醚、异氟醚、七氟醚、地氟醚、N2O和氙气,相互作用包括相加、协同、拮抗、等效。如果可能,数据将应用分数分析和响应面分析。

结果:在不同药物种类之间大多数相互作用是协同作用。氯胺酮是个例外,其主要相互作用是相加或拮抗作用。吸入麻醉药和静脉麻醉药之间主要为协同作用,但也有相加作用或在某些情况下可能是拮抗作用,如笑气和异氟醚。

结论:除了氯胺酮,静脉麻醉药通常作用于不同位点产生协同作用,吸入麻醉药通常和静脉麻醉药之间是协同作用,但吸入麻醉药之间不呈协同作用。

(潘方立 译 陈杰 校)

BACKGROUND: Drug interactions may reveal mechanisms of drug action: additive interactions suggest a common site of action, and synergistic interactions suggest different sites of action. We applied this reasoning in a review of published data on anesthetic drug interactions for the end-points of hypnosis and immobility.

METHODS: We searched Medline for all manuscripts listing propofol, etomidate, methohexital, thiopental, midazolam, diazepam, ketamine, dexmedetomidine, clonidine, morphine, fentanyl, sufentanil, alfentanil, remifentanil, droperidol, metoclopramide, lidocaine, halothane, enflurane, isoflurane, sevoflurane, desflurane, N2O, and Xe that contained terms suggesting interaction: interaction, additive, additivity, synergy, synergism, synergistic, antagonism, antagonistic, isobologram, or isobolographic. When available, data were reanalyzed using fraction analysis or response surface analysis.

RESULTS: Between drug classes, most interactions were synergistic. The major exception was ketamine, which typically interacted in either an additive or infra-additive (antagonistic) manner. Inhaled anesthetics typically showed synergy with IV anesthetics, but were additive or, in the case of nitrous oxide and isoflurane, possibly infra-additive, with each other.

CONCLUSIONS: Except for ketamine, IV anesthetics acting at different sites usually demonstrated synergy. Inhaled anesthetics usually demonstrated synergy with IV anesthetics, but no pair of inhaled anesthetics interacted synergistically.

 

异丙酚对肝L02细胞的保护作用,激活细胞外信号调节激酶通路减少因过氧化氢引起的细胞凋亡

Propofol Protects Hepatic L02 Cells from Hydrogen Peroxide-Induced Apoptosis via Activation of Extracellular Signal-Regulated Kinases Pathway

Hao Wang, MD, PhD*, Zhanggang Xue, MD*, Qiong Wang, MS{dagger}, Xiaochen Feng, MS{dagger}, and Zonghou Shen, PhD{dagger}

From the *Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; and {dagger}Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China.

Anesth Analg 2008 107: 534-540.

 

背景:在一些器官中异丙酚可以通过抑制缺血/再灌注所造成的损伤来保护细胞,但很少有关于它对肝上皮细胞作用的报告。作者研究了经异丙酚预处理的肝L02细胞在过氧化氢(H2O2)氧化应激情况下的效应,判断在这个过程中是否存在细胞外信号调节激酶(ERK)通路。

方法:预处理或未预处理过的人类肝L02细胞暴露在H2O2中,根据TUNEL测定、半胱天冬酶3、多形核白细胞ADP-核糖聚合酶(PARP)的分裂,来评估细胞凋亡的变化。ERK1/2的激活,丝裂原激活蛋白激酶//ERL激酶1/2(MEK1/2)由西方墨迹分析法量度。Bcl-2,Bcl-xL,Bad,BaxmRNA的表达用实时定量的逆转录酶聚合酶链反应来定量。

结果:异丙酚预处理可以减少由过氧化氢引起的肝内L02细胞凋亡、半胱天冬酶3PARP分裂的总数。肝L02细胞单独用异丙酚(0.01-0.3mM)处理,ERKMEK的剂量依存性激活的最小剂量,这种激活可以在0.5h内被检测到, 4h时到达下限<50%。特异抑制剂PD98059可完全抑制ERK的激活并加重细胞凋亡的程度。异丙酚处理可抑制凋亡基因BadBax mRNA表达,且这种反应可部分被PD98059逆转。

结论:这些研究结果表明,异丙酚对过氧化氢应激的肝L02细胞的具有保护作用,部分通过激活MEK-ERK通路,从而进一步抑制BadBax的表达来实现的。

(怀晓蓉 译 陈杰 校)

BACKGROUND: Propofol protects cells against ischemia/reperfusion injury in several organs, but there are few reports of its effect on liver epithelial cells. We investigated the effect of propofol preconditioning on human hepatic L02 cells under hydrogen peroxide (H2O2)-induced oxidative stress and attempted to determine whether the extracellular signal-regulated kinases (ERK) pathway is involved in this process.

METHODS: Preconditioned or nonpreconditioned human hepatic L02 cells were exposed to H2O2 and the changes of apoptosis were evaluated by TUNEL assay, Caspase-3 and poly ADP-ribose polymerase (PARP) cleavage. Activation of ERK1/2 and mitogen-activated protein kinase//ERK Kinase 1/2 (MEK1/2) was measured by Western blot analysis. The mRNA expression of Bcl-2, Bcl-xL, Bad, and Bax was quantified by real-time quantitative reverse transcriptase polymerase chain reaction.

RESULTS: Propofol preconditioning reduced the population of apoptotic cells and Caspase-3 and PARP cleavage induced by H2O2 inhepatic L02 cells. L02 cells treated with propofol (0.01–0.3 mM) alone, led to a dose-dependent activation of ERK and MEK, and such activation was detected within 0.5 h and eventually declined to <50% at 4 h. The addition of the specific inhibitor PD98059 completely abolished the activation of ERK and aggravated the extent of apoptosis. Moreover, propofol treatment repressed the mRNA expression of proapoptotic genes Bad and Bax, and this repression could be partly reversed by PD98059.

CONCLUSIONS: These findings demonstrate that propofol protects hepatic L02 cells from H2O2-induced apoptosis, partly through activating the MEK-ERK pathway and further suppressing Bad and Bax expression.

 

冠状动脉支架:第一部分 经皮冠状动脉介入治疗的进展

Coronary Artery Stents: Part I. Evolution of Percutaneous Coronary Intervention

Lisa T. Newsome, MD, DMD*, Michael A. Kutcher, MD{dagger}, and Roger L. Royster, MD*

From the Departments of *Anesthesiology, and {dagger}Cardiology (Interventional Cardiology), Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Anesth Analg 2008 107: 552-569.

 

在过去的三十年,随着经皮腔内冠状动脉血管成形术和经皮腔内斑块旋切术,裸金属支架和药物洗脱支架的快速发展,心脏介入技术在冠状动脉性心脏病的治疗方面有了显著进展。裸金属支架(BMS)通过血管成形术维持血管腔的直径防止其塌陷。然而,裸金属支架会引起内膜增生从而产生支架内再狭窄,超过20%的病人需要再次行介入治疗,通过药物洗脱支架(DES)(包括西罗莫斯洗脱支架和紫杉醇洗脱支架)抑制血管内皮增生来防止再狭窄。然而,药物洗脱支架对血管内皮细胞生长的延迟在某种程度上会引起支架血栓形成。45%的病人死亡率与支架血栓形成相关。过早停用抗血栓治疗药物,尤其是氯吡格雷通常会引起支架血栓形成。60%的病人由于使用了未经批准使用的支架同样会增加了支架血栓形成的发生率。在裸金属支架和药物洗脱支架治疗中,氯吡格雷和阿司匹林都是预防支架血栓形成的基础性药物。关于两联抗血栓治疗的药物最佳持续使用时间仍有争议。食品药物管理局和美国心脏协会/美国大学的心脏学家和各个相关学科的学者对两联抗血栓治疗持续时间的建议为:使用药物洗脱支架的患者最佳治疗时间为一年,对使用裸金属支架的患者为六个月。所有使用冠脉支架治疗的患者必须终身服用阿司匹林药物。随着经皮腔内冠状动脉血管成形术作为冠状动脉硬化治疗手段的引入,经皮冠状动脉介入治疗经历了从单一的球囊扩张导管到复杂机械化的管腔内支架的戏剧化转变。这一系列的进展影响着围术期的用药。本文作者在第一部分回顾了经皮冠状动脉介入治疗的进展并进行关于经皮腔内冠状动脉血管成形术和冠脉支架术的讨论;在第二部分作者将对冠状动脉支架对非心脏病性外科手术术中问题和使用策略进行了讨论。

(赵嫣红 译 陈杰 校)

The subspecialty of interventional cardiology has made significant progress in the management of coronary artery disease over the past three decades with the development of percutaneous coronary transluminal angioplasty, atherectomy, and bare-metal and drug-eluting stents (DES). Bare-metal stents (BMS) maintain vessel lumen diameter by acting as a scaffold and prevent collapse incurred by angioplasty. However, these devices cause neointimal hyperplasia leading to in-stent restenosis and requiring reintervention in more than 20% of patients by 6 mo. DES (sirolimus and paclitaxel) prevent restenosis by inhibiting neointimal hyperplasia. However, DESs also delay endothelialization, causing the stents to remain thrombogenic for an extended, yet unknown, period of time. Late stent thrombosis is associated with a 45% mortality rate. Premature discontinuation of antiplatelet therapy, particularly clopidogrel, is the strongest predictor of stent thrombosis. Sixty percent of patients receive stents for off-label (unapproved) indications, which also increases the frequency of stent thrombosis. Clopidogrel and aspirin are the cornerstone of therapy in the prevention of stent thrombosis in both BMS and DES. Recommendations pertaining to the optimal duration of dual-antiplatelet therapy have been debated. Both the Food and Drug Administration and the American Heart Association/American College of Cardiologists, in association with other major societies, have made recommendations to extend the duration of dual-antiplatelet therapy in patients with DES to 1 yr. The 6-wk duration of dual-antiplatelet therapy in patients with BMS remains unchanged. All patients with coronary stents must remain on life-long aspirin monotherapy. Since the introduction of percutaneous transluminal coronary angioplasty for the treatment of coronary atherosclerosis, the practice of percutaneous coronary intervention has undergone a dramatic transformation from simple balloon dilation catheters to sophisticated mechanical endoprostheses. These advancements have impacted the practice of perioperative medicine. In this series of two articles, in Part I we will review the evolution of percutaneous coronary intervention and discuss the issues associated with percutaneous transluminal coronary angioplasty and coronary stenting; in Part II we will discuss perioperative issues and management strategies of coronary stents during noncardiac surgery.

 

胸内血容指数可作为评估急性循环衰竭危重病人机体容量反应的一个指标:与中心静脉压的比较

The Intrathoracic Blood Volume Index as an Indicator of Fluid Responsiveness in Critically Ill Patients with Acute Circulatory Failure: A Comparison with Central Venous Pressure

Laurent Muller, MD, MSc*{dagger}, Guillaume Louart, MD*{dagger}, Christian Bengler, MD*, Pascale Fabbro-Peray, MD{ddagger}, Julie Carr, MD*, Jacques Ripart, MD, PhD*{dagger}, Jean-Emmanuel de La Coussaye, PhD, MD*{dagger}, and Jean-Yves Lefrant, MD, PhD*{dagger}

From the *Division Anesthésie Réanimation Douleur Urgences, Groupe Hospitalo-Universitaire Caremeau, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9. Faculté de Médecine, Université Montpellier 1; {dagger}Equipe d’Accueil 2992, Laboratoire de physiologie cardiovasculaire et d’anesthésie expérimentale, Faculté de Médecine, Groupe Hospitalo-Universitaire Caremeau, Place du Professeur Robert Debré, 30 029 Nîmes; and {ddagger}Département d’Information médicale, Groupe Hospitalo-Universitaire Caremeau, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9. Faculté de Médecine, Université Montpellier 1.

Anesth Analg 2008 107: 607-613.

 

背景:胸内血容指数(ITBVI)和中心静脉压(CVP)常用于评估急性循环衰竭危重病人(收缩压小于90 mmHg或者需要血管升压药的病人)的液体容量,然而它们之间未曾比较。

方法:在这项前瞻性干预研究中,作者选择35名(其中男性21名)镇静下行机械辅助呼吸且监测心排血量(采用漂浮导管,温度稀释法)的急性循环衰竭病人。机体容量反应定义为休克指数(心输出量/心率/体表面积)升高大于15%。记录ITBVICVP变化特征曲线。

结果51%患者在液体冲击试验后休克指数升高大于等于15%(为阳性反应)。基础血流动力学数据在阳性者与阴性者之间无差异。ITBVI的特征曲线下面积是0.64(95%CI0.46-0.80),而CVP0.6895CI0.46-0.80),两者无统计学差异(P0.73)。CVPITBVI的最佳甄别阈分别是9mmHg.(灵敏度=61%,特异性=82%)和928 mmHg(灵敏度=78%,特异性=53%)。

结论ITBVI在评估急性循环衰竭危重病人的液体容量方面,与CVP有着相似的价值。

(叶乐 译 陈杰 校)

BACKGROUND: The intrathoracic blood volume index (ITBVI) and central venous pressure (CVP) are routinely used to predict fluid responsiveness in critically ill patients with acute circulatory failure (systolic blood pressure <90 mm Hg or vasopressor requirement). However, they have never been compared.

METHODS: In this prospective interventional study, we included 35 (21 men) mechanically ventilated and sedated patients with acute cardiovascular failure requiring cardiac output measurement (transpulmonary thermodilution technique). Fluid responsiveness was defined as an increase in stroke index (cardiac output/heart rate/body surface area) ≥15%. Receiver operating characteristic curves were generated for ITBVI and CVP.

RESULTS: Fluid challenge induced a stroke index increase ≥15% in 18 (51%) patients (responders). At baseline, no studied hemodynamic variables were different between responders and nonresponders. The areas under the receiver operating characteristic curves were 0.64 [95% CI: 0.46–0.80] for ITBVI and 0.68 [95% CI: 0.50–0.83] for CVP, without any statistical difference (P = 0.73). The best cut-off values for CVP and ITBVI were 9 mm Hg (sensitivity = 61%; specificity = 82%) and 928 mL · m–2 (sensitivity = 78%; specificity = 53%).

CONCLUSION: ITBVI is similar to CVP in its ability to predict fluid responsiveness in critically ill patients with acute circulatory failure.

 

随机药物抽检减少麻醉住院医师药物依赖发生率:来自一个研究方案的初步结果

Random Drug Testing to Reduce the Incidence of Addiction in Anesthesia Residents: Preliminary Results from One Program

Michael G. Fitzsimons, MD, Keith H. Baker, MD, PhD, Edward Lowenstein, MD, and Warren M. Zapol, MD

From the Department of Anesthesia and Critical Care, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts.

Anesth Analg 2008 107: 630-635.

 

麻醉住院医师的药物滥用率约为1%-2%,几乎80%的研究方案中有一个或多个住院医师存在上述问题。教育和药物控制未能减少药物滥用的发生率。麻醉医生职业责任为患者提供良好用药.作者建立一个方案通过随机抽验麻醉科住院医师尿液来尝试减少药物滥用发生率。尽管有逻辑上和文化上问题,作者认为这方案易于施行。更大的多机构的研究是必须的以确定是否需制定随机尿检以减少麻醉住院医师的药物滥用发生率。

(丁俊云 译 陈杰 校)

Substance abuse occurs in approximately 1%–2% of anesthesia residents and nearly 80% of programs have had one or more resident (s) with such a problem. Education and control efforts have failed to reduce the frequency of substance abuse. Anesthesia providers have a professional obligation to be drug-free for the well being of their patients. We have instituted a program of preplacement and random urine testing of residents in anesthesiology in an attempt to decrease the incidence of substance abuse. We demonstrate that such a program is feasible, despite logistic and cultural obstacles. Larger multi-institutional studies will be required to determine whether instituting a program of random urine testing decreases the incidence of substance abuse in anesthesiology residents.

 

3-甲基巴豆酰辅酶A羧化酶缺乏症病人的麻醉

Anesthetic Management of a Patient with 3-Methylcrotonyl-CoA Carboxylase Deficiency

Karen A. Robbins, MD, and Elias N. León-ruiz, MD

From the Department of Anesthesiology and Perioperative Medicine, University Hospitals Case Medical Center, Cleveland, Ohio.

Anesth Analg 2008 107: 648-650.

 

有先天性代谢障碍的病人在围术期需特殊考虑。下文的病例报告中,作者成功处理了一例3-甲基巴豆酰辅酶A羧化酶缺乏症的病人,疾病导致继发性肉毒碱缺乏和β 氧化功能障碍。患者可能存在潜在的心肌病,在应激状态下有代谢失代偿、酸中毒、低血糖的危险。

(杜唯佳 译 陈杰 校)

Patients with inborn errors of metabolism require special considerations in perioperative care. In the following case report, we describe the successful management of a patient with 3-methylcrotonyl-CoA carboxylase deficiency, a deficit that causes a secondary carnitine deficiency and impaired β oxidation. Patients may have significant underlying cardiomyopathy, and are at risk for metabolic decompensation, acidosis, and hypoglycemia during periods of stress.

 

乳癌术后病人自控椎旁镇痛的可行性:两种方法的前瞻性、随机双盲研究的比较

The Feasibility of Patient-Controlled Paravertebral Analgesia for Major Breast Cancer Surgery: A Prospective, Randomized, Double-Blind Comparison of Two Regimens

Jennifer McElwain, FCARCSI*, Noelle M. Freir, FCARCSI*, Crina L. Burlacu, FCARCSI*, Denis C. Moriarty, FCARCSI*, Daniel I. Sessler, MD{dagger}, and Donal J. Buggy, MD, MSc, DME, FRCPI, FCARCSI, FRCA*{ddagger}

From the *Department of Anaesthesia, Mater Misericordiae University Hospital, Dublin, Ireland; {dagger}Department of Outcomes Research, The Cleveland Clinic, Cleveland, Ohio; {ddagger}National Cancer Screening Service, Eccles Unit, Dublin, Ireland.

Anesth Analg 2008 107: 665-668.

 

背景:椎旁镇痛用于乳房术后是有效的。PCIA或者PCEA用于术后镇痛的效果已经被很好的证明。本研究目的是将椎旁镇痛应用到病人自控镇痛中,并且评估两种不同方法的效应和耐受性。

方法:参与此次随机双盲试验的是乳癌术后患者,随机分成两组进行两种不同方法的自控椎旁镇痛:19名病人接受0.2%的左旋布比卡因,持续剂量8ml/hPCA剂量3ml,锁定时间15分(15分锁定组);18名病人接受0.2%的左旋布比卡因,持续剂量4ml/hPCA剂量8ml,锁定时间30分(30分锁定组)。主要预后指标一是动态疼痛评分(视觉疼痛评分量表),间隔4小时一次,进行36个小时。另一指标是静息疼痛评分,包括援救镇痛药物的需要量,左旋布比卡因的用量,需要量,PCA剂量和患者的满意度。

结果:静息和动态的疼痛评分分组进行比较。15分锁定组中有2名患者和30分锁定组有5名患者要援救镇痛药物(P=0.23)。两组病人接受的左旋布比卡因的量分别是15分锁定组400±95ml30分锁定组330±130mlP=0.012)。15分锁定组病人需要单次注射次数是75±16次,30分锁定组为69±14次(P=0.4)。然而,15分锁定组病人接受的PCA次数是39±22次,30分锁定组则只有24±16次(P=0.02)。收缩压,心率,呼吸频率,镇静评分,恶心,止吐药物的需要量和满意度两组是相似的。

结论:乳癌术后病人自控椎旁镇痛的两种方法都可以提供满意的镇痛效果并具有和很好耐受性。

(舒慧刚 译 陈杰 校)

BACKGROUND: Paravertebral analgesia is useful for breast surgery. Patient controlled analgesia by IV or epidural routes is well established for delivering postoperative analgesia. Our objective was to apply patient control to paravertebral analgesia and evaluate the efficacy and tolerability of two distinct dosing regimens.

METHODS: Patients undergoing major breast cancer surgery were recruited for this prospective, double-blind, randomized trial of two patient-controlled paravertebral analgesia regimens: 19 patients received levobupivacaine 0.2% at 8 mL/h with 3-mL bolus and 15-min lockout (15-min lockout group); 18 received levobupivacaine 0.2% at 4 mL/h with 8-mL bolus and 30-min lockout (30-min lockout group). Our primary outcome was dynamic pain scores (visual analog scale) at 4-hourly intervals for 36 h. Secondary outcomes were resting pain scores, rescue analgesia requirements, volume of levobupivacaine administered, demands for levobupivacaine, levobupivacaine boluses received, and patient satisfaction.

RESULTS: Resting and dynamic pain scores were comparable in the groups. Two 15-min lockout patients and five 30-min lockout patients required rescue analgesia (P = 0.23). Patients received 400 ± 95 mL and 330 ± 130 mL levobupivacaine in 15-min and 30-min lockout groups, respectively (P = 0.012). The 15-min lockout group requested a bolus 75 ± 16 times; the 30-min lockout group requested it 69 ± 14 times (P = 0.40). However, the 15-min lockout group received 39 ± 22 boluses and the 30-min lockout group only 24 ± 16 (P = 0.02). Systolic pressure, heart rate, respiratory rate, sedation scores, nausea, antiemetic requirement, and satisfaction scores were similar in each group.

CONCLUSIONS: Patient-controlled paravertebral analgesia for breast cancer surgery, with either regimen, provided satisfactory analgesia and was well tolerated.

 

长时使用吗啡损害小鼠血管形成和内皮原细胞的活动

Prolonged Use of High-Dose Morphine Impairs Angiogenesis and Mobilization of Endothelial Progenitor Cells in Mice

Chen-Fuh Lam, MD, PhD*, Pei-Jung Chang, MD*, Yu-Sheng Huang, MD*, Yen-Hui Sung, MD*, Chien-Chi Huang, BS*, Ming-Wei Lin, MS*{dagger}, Yen-Chin Liu, MD, MS*, and Yu-Chuan Tsai, MD*

From the *Department of Anesthesiology; and {dagger}Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan.

Anesth Analg 2008 107: 686-692.

 

背景:吗啡是一种治疗伤口疼痛最普通的处方药之一,本研究用一个带有受伤创口的小鼠做模型,观察大剂量吗啡对血管发生和内皮原细胞活动的影响。

方法:在小鼠身上制一切开伤口,用安慰剂或吗啡(20mg/kg, ip)治疗14天。通过测试用药前伤口的面积和用药后伤口面积的比例来比较伤口的愈合,通过鲁米若增强发光剂来检测伤口区超氧化物阴离子的浓度, 分离循环的单核细胞并计内皮原细胞数目(确定为CD34+/CD133+细胞),用Matrigel(基质胶)测定法测定在体和离体经过吗啡治疗后血管形成情况。

结果:吗啡组比对照组小鼠伤口愈合减慢,伤口周围的超氧化物离子高。吗啡减少伤口内皮原细胞的活动数目,基质胶测定法显示吗啡损害动物血管形成,用吗啡处理过的培养的内皮细胞显示动物血管发生受损及毛细血管形成减少。

结论:大剂量吗啡损害血管发生,增强系统氧化应激增强及内皮原细胞活动受损。本研究强调系统给予大剂量吗啡对血管发生存在潜在的有害作用。

(刘世文 译 陈杰 校)

BACKGROUND: Morphine is one of the most commonly prescribed analgesics for treating wound pain. Using a mouse model of excisional wound injury, we determined the effects of high-dose morphine on angiogenesis and mobilization of endothelial progenitor cells.

METHODS: An excisional wound was created on mice treated with placebo or morphine (20 mg/kg, i.p. injection for 14 days). Wound healing was compared by measuring the final-to-initial wound area ratio. Generation of superoxide anions in the wound was determined by luminol-enhanced chemiluminescence. Circulating mononuclear cells were isolated and measured for endothelial progenitor cell (defined as CD34+/CD133+ cell) counts. In vivo and in vitro measurements of angiogenesis after morphine treatment were performed using the Matrigel assay.

RESULTS: Mice treated with morphine had reduced wound closure and higher wound superoxide ions concentrations than control mice. Morphine reduced the number of postwound circulating endothelial progenitor cells. Matrigel assay showed impaired angiogenesis in animals and reduced capillary tube formation in cultured endothelial cells treated with morphine.

CONCLUSION: High-dose morphine impaired angiogenesis, increased systemic oxidative stress, and impaired mobilization of endothelial progenitor cells. This study emphasizes the potential detrimental effect of high-dose morphine on angiogenesis after systemic administration.

 

影响局麻药在硬膜外麻醉神经阻滞平面的因素及腰段和胸段硬膜外麻醉的比较

Factors Affecting the Distribution of Neural Blockade by Local Anesthetics in Epidural Anesthesia and a Comparison of Lumbar Versus Thoracic Epidural Anesthesia

W. Anton Visser, MD, PhD*, Ruben A. Lee, BE(Hons){dagger}, and Mathieu J. M. Gielen, MD, PhD{ddagger}

From the *Department of Anesthesiology, Intensive Care and Pain Management, Amphia Hospital, Breda; {dagger}Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Technical University of Delft, Delft; and {ddagger}Department of Anesthesiology, University Medical Center Nijmegen, Nijmegen, The Netherlands.

Anesth Analg 2008 107: 708-721.

 

在不同的个体中,一定剂量的局麻药在硬膜外腔扩散的感觉阻滞是有个体差异的,影响因素仍有争论。基于最近关于硬膜外神经阻滞的研究结果,特别是胸段的硬膜外麻醉,作者发现局麻药的总容量似乎在决定感觉平面、交感神经、运动神经阻滞等发面起主要作用,硬膜外针或导管的位置决定阻滞神经的类型。年龄可能与感觉阻滞平面有一定的相关性,胸部的硬膜外神经阻滞比腰部更为明显。病人的特征及技术细节,如病人的体位、麻醉操作方式及注射速度,只能在感觉障碍分布方面起到很小的作用,或者说这些影响是不确定的。然而,很多病人因素和技术因素的结合可以帮助预测局麻药剂量的需求。基于这些研究结果,作者认为可以根据不同外科手术在镇痛和交感阻滞要求而优化硬膜外穿刺点。

(张磊 译 陈杰 校)

The spread of sensory blockade after epidural injection of a specific dose of local anesthetic (LA) differs considerably among individuals, and the factors affecting this distribution remain the subject of debate. Based on the results of recent investigations regarding the distribution of epidural neural blockade, specifically for thoracic epidural anesthesia, we noted that the total mass of LA appears to be the most important factor in determining the extent of sensory, sympathetic, and motor neural blockade, whereas the site of epidural needle/catheter placement governs the pattern of distribution of blockade relative to the injection site. Age may be positively correlated with the spread of sensory blockade, and the evidence is somewhat stronger for thoracic than for lumbar epidural anesthesia. Other patient characteristics and technical details, such as patient position, and mode and speed of injection, exert only a small effect on the distribution of sensory blockade, or their effects are equivocal. However, combinations of several patient and technical factors may aid in predicting LA dose requirements. Based on these results, we have also formulated suggested epidural insertion sites that may optimize both analgesia and sympathicolysis for various surgical indications.

预防性应用止吐药物对呕吐高危患者出院后恶心呕吐发生率及恢复期生活功能性质量的影响:一项前瞻、随机、双盲比较两种预防性止吐方案的试验研究

Antiemetic Prophylaxis for Postdischarge Nausea and Vomiting and Impact on Functional Quality of Living During Recovery in Patients with High Emetic Risks: A Prospective, Randomized, Double-Blind Comparison of Two Prophylactic Antiemetic Regimens

Peter H. Pan, MSEE, MD, Sherman C. Lee, MD, and Lynne C. Harris, BSN

From the Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Anesth Analg 2008; 107:429-438

背景:比较两种预防性应用止吐药物的方法预防出院后恶心呕吐的效果以及对患者恢复期生活质量的影响。

方法:64例行门诊妇科手术且存在呕吐高危风险的女性患者随机分为两组:试验组术中静脉注射地塞米松8 mg及恩丹司琼4 mg,随后在出院时及术后第1天、第二天早晨分次口服8 mg恩丹司琼片剂。对照组术中只静脉注射恩丹司琼4 mg。在麻醉后恢复室及出院后通过电话随访5天每日1次评价恶性呕吐症状以及疼痛的发生率及严重程度。用一项修订的呕吐功能性生活指数来评估对恢复期生活质量的影响。

结果:共有60例患者完成了这项实验,每组各30例。出院后,从麻醉后第8h到第120h期间恶心的发生率对照组和试验组分别为57%和20%,呕吐的发生率两组分别为20%和3%(P < 0.05)。33%的试验组患者及60%的对照组患者均报告有呕吐症状,对其生活质量产生了不良影响(P < 0.05)。

结论:与单次术中静脉注射恩丹司琼预防性应用相比,术中加地塞米松及术后每天一次恩丹司琼能显著降低出院后恶心呕吐的发生率,并减少对术后恢复期前5天生活质量的不良影响。

(邱郁薇 译 马皓琳 李士通 校)

BACKGROUND: We compared two antiemetic prophylaxis regimens, their efficacy for preventing postdischarge nausea and vomiting, and their impact on quality of living, during recovery.

METHODS: Sixty-four women undergoing outpatient gynecological surgery and at high risk for emesis were randomized into one of two groups. The study group received intraoperative IV dexamethasone 8 mg and ondansetron 4 mg, followed with an 8 mg oral disintegrating ondansetron tablet, to be taken on discharge and in the morning of postoperative days 1 and 2. The control group received only the IV ondansetron 4 mg intraoperatively. The incidence and severity of emetic symptoms and pain were assessed while patients were in the recovery room and via telephone and patient diary for 5 days after discharge. A modified functional living index of emesis was used to assess the impact on quality of living during recovery.

RESULTS: Sixty patients, 30 in each group, completed the study. The incidences for postdischarge nausea were 57% and 20%, and for postdischarge vomiting 20% and 3% in the control and study groups, respectively, for the period between the 8th and 120th hours postanesthesia (P < 0.05). Thirty-three percent of the study and 60% of the control group reported that emetic symptoms negatively affected their quality of living (P < 0.05).

CONCLUSIONS: When compared with a single dose of intraoperative IV ondansetron prophylaxis, our study regimen of additional intraoperative dexamethasone and once a day ondansetron significantly reduced the incidence of postdischarge nausea and vomiting and its negative impact on quality of living during the first 5 days of recovery.


 

评价3种不同剂量的帕洛诺司琼与安慰剂在术后72小时内防止术后恶心呕吐的有效性和安全性的随机双盲研究

A Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Three Different Doses of Palonosetron Versus Placebo in Preventing Postoperative Nausea and Vomiting Over a 72-Hour Period

Anthony L. Kovac, MD*, Leopold Eberhart, MD{dagger}, Jan Kotarski, MD{ddagger}, Giuseppina Clerici, MD§, Christian Apfel, MD, PhD||, and The Palonosetron 04-07 Study Group

From the *Department of Anesthesiology, University of KS Medical Center, KS City, Kansas; {dagger}Department of Anesthesia and Intensive Care Medicine, Philipps-University of Marburg, Marburg, Germany; {ddagger}First Department of Gynecological Surgery, University School of Medicine, Lublin, Poland; §Research and Development Department, Helsinn Healthcare SA, Lugano, Switzerland; and ||Perioperative Clinical Research Core, Department of Anesthesia and Perioperative Care, University of CA San Francisco, San Francisco, CA.

Anesth Analg 2008; 107:439-444

背景:我们设计这个多中心、随机、双盲的研究来评估3种不同剂量的帕洛诺司琼与安慰剂对于术后72小时内术后恶心呕吐(PONV)的发生及严重程度影响的有效性和安全性。

方法:行择期妇科或者乳腺手术的女性患者,根据另外2个PONV风险因素(不吸烟状况和PONV和/或晕动病病史)分层。544名有以上有1个或2个风险因素的患者在麻醉诱导前即刻随机静脉注射一种剂量的帕洛诺司琼(0.025 mg、0.050 mg或0.075 mg)或安慰剂。术后0-24小时和24-72小时两时间段的主要有效性指标为完全有效(CR:没有呕吐并且没有使用缓解药物)。

结果:安慰剂和0.075 mg帕洛诺司琼的术后0-24小时CR率为36%和56% (P = 0.001),24-72小时CR率为52%和70% (P = 0.002),0-72小时CR率为36%和52% (P = 0.010)。0.075 mg帕洛诺司琼与安慰剂相比在0-24小时内(P < 0.001)恶心程度较小(接近“轻度”或“无”),而且显著延迟了出现呕吐时间(P = 0.002)和治疗失败时间(P = 0.004)的中位数。尽管在统计学上0.025 mg和0.050 mg剂量的帕洛诺司琼CR率在0-24小时和24-72小时时间段内并不优于安慰剂,但是较低的剂量可以在0-24小时内缓解恶心的严重程度(P = 0.040和P = 0.004)。

结论:单次静脉注射0.075mg帕洛诺司琼能有效地缓解入院手术患者术后恶心的严重程度,并且推迟呕吐和治疗失败的时间;低剂量就不是那么有效。

(唐亮 译  马皓琳 李士通 校)

BACKGROUND: We designed this multicenter, randomized, double-blind study to assess the efficacy and safety of three doses of palonosetron, compared with placebo, on the incidence and severity of postoperative nausea and vomiting (PONV) in inpatients for 72 h after surgery.

METHODS: Female patients undergoing either elective gynecological or breast surgery were stratified according to two additional PONV risk factors: nonsmoking status and history of PONV and/or motion sickness. Five hundred forty-four patients with one or both of these risk factors were randomized to receive one of the three doses of IV palonosetron (0.025 mg, 0.050 mg, 0.075 mg) or placebo immediately before induction of anesthesia. The primary efficacy end-point was complete response (CR: no emesis and no use of rescue medications) evaluated at the 0–24 and 24–72 h time intervals after surgery.

RESULTS: CR rates for placebo and palonosetron 0.075 mg were 36% and 56% for 0–24 h (P = 0.001), 52% and 70% for 24–72 h (P = 0.002) and 36% and 52% (P = 0.010) for the 0–72 h postoperative interval. Palonosetron 0.075 mg was associated with less intense nausea (e.g., toward "mild" or "none") versus placebo during the 0–24 h (P < 0.001) time interval and significantly delayed median time to emesis (P = 0.002) and treatment failure (P = 0.004). Although CR rates for both the 0.025 mg and 0.050 mg palonosetron doses were not statistically superior to placebo for the 0–24 h or 24–72 h periods, both lower doses reduced nausea severity during the 0–24 h period (P = 0.040 and P = 0.004).

CONCLUSION: A single 0.075-mg IV dose of palonosetron effectively reduced the severity of nausea and delayed the time to emesis and treatment failure in the inpatient surgical setting; lower doses were not as effective.


 

病人危险因素与其术后早期以及后期发生呕吐症状的相关性分析

The Relationship Between Patient Risk Factors and Early Versus Late Postoperative Emetic Symptoms

Paul F. White, PhD, MD, FANZCA, Ozlem Sacan, MD, Nina Nuangchamnong, MS, Tiffany Sun, MS, and Matthew R. Eng, MS

From the Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, Texas.

Anesth Analg 2008; 107:459-463

背景术后恶心呕吐(PONV)仍然是择期手术术后常见的并发症,因此常常对具有发生PONV的已知危险因素的病人预防性应用止吐药物。我们设计这次前瞻性观察研究的目的就是来评价病人发生PONV的常见危险因素与其术后早期(0–24 h)以及晚期(24–72 h)发生呕吐症状的关联性。

方法:130名拟行择期腹腔镜手术(n = 88)或整形手术(n = 42)的病人根据Apfel风险评分系统算出其发生PONV的风险分数。Apfel风险评分系统给女性、不吸烟者、有PONV或晕动病史以及术后阿片类药物的使用四个危险因素各记一分。假定所有病人都将在术后接受阿片类镇痛药。所有病人预防性接受0、1、2或3种止吐药物。术后分别在0-6h,6-24h以及24-72h时段内评价恶心呕吐的发生情况以及需要止吐药物来补救治疗的情况。另外,用标准化的病人问卷来评价PONV对正常日常生活活动恢复的影响。

结果:在Apfel风险评分分别为2、3和4分的组中分别有87%、90%和95%病人预防性应用一种或更多种的止吐药。当危险因素为3个或者4个时,分别有56%和 75%的病人接受了≥2种止吐药。在术后0-6h时段内,三个危险因素组和四个危险因素组分别有11% 和22%的病人发生呕吐,而两个危险因素组有6%的病人发生呕吐;在术后6–24 h时段内,呕吐的发生率分别为13%和27% (比0%)。然而,在术后24–72 h时段内,三组呕吐的发生率均低且组间没有差别(分别为9%、 5%和11%)。术后0–6 h 以及6–24 h时段内高危险因素组中中到重度恶心的发生率增高(分别为19%–28%比6% 和 20%–30%比9%)。然而,术后24–72 h时段内三个危险因素组和四个危险因素组恶心的发生率与两个危险因素组没有差别(5%和8%比6%)。四个危险因素组对补救止吐药的需要和呕吐症状对正常活动的干扰与两个和三个危险因素组相比明显提高。

结论:尽管常常预防性使用多种止吐药物,Apfel风险评分为3或4(与2相比)仍与术后首个24小时内较高的呕吐发生率相关。然而,后期(24–72 h)呕吐症状的发生率低且似乎与病人的Apfel风险评分没有关系。

(吴进 译  马皓琳 李士通 校)

BACKGROUND: Postoperative nausea and vomiting (PONV) remain common complications after elective surgery. Prophylactic antiemetic drugs are frequently administered to patients with well known risk factors for developing PONV. We designed this prospective observational study to assess the relationship between common patient risk factors for developing PONV and the occurrence of early (0–24 h) versus late (24–72 h) emetic symptoms.

METHODS: One hundred thirty patients undergoing elective laparoscopic (n = 88) or plastic (n = 42) surgery were assigned a risk score for developing PONV based on the Apfel risk scoring system, which assigns one point each for female gender, nonsmoking status, history of PONV or motion sickness, and postoperative opioid use. It was assumed that all patients would receive an opioid analgesic in the postoperative period. The patients received 0, 1, 2, or 3 antiemetic drugs for prophylaxis. The occurrence of nausea, vomiting, and need for rescue antiemetics was assessed at specific time intervals from 0 to 6, 6–24, and 24–72 h after surgery. In addition, the impact of PONV on recovery of normal activities of daily living was assessed using a standardized patient questionnaire.

RESULTS: One or more prophylactic antiemetics were administered to 87%, 90%, and 95% of the patients in the two, three, and four Apfel risk-factor groups, respectively. In the presence of three or four risk factors, ≥2 antiemetics were administered to 56% and 75% of the patients, respectively. Vomiting was reported in 11% and 22% of patients in the three and four risk factor groups compared with 6% in the two risk factor group at 0–6 h, and 13% and 27% (vs 0%) at 6–24 h, respectively. However, in the 24–72 h postoperative period, the incidences of emesis were low and did not differ in the three risk groups (9%, 5%, and 11%, respectively). The occurrence of moderate-to-severe nausea was increased in the higher risk groups at 0–6 h and 6–24 h (19%–28% vs 6% and 20%–30% vs 9%, respectively). However, the incidences of nausea in the 24–72 h period in the three and four risk factor groups were not different from the two-risk factor group (5% and 8% vs 6%, respectively). The need for rescue antiemetics and interference of emetic symptoms with normal activities was greater in the four risk factor group compared with the two and three risk factor groups.

CONCLUSION: Despite the frequent use of multiple antiemetic drugs for prophylaxis, an Apfel risk score of three or four (vs 2) was associated with a higher incidence of emetic sequelae in the first 24 h after surgery. However, the occurrence of late (24–72 h) emetic symptoms was low and appeared to be unrelated to the patient's Apfel risk score.



全麻药对三种配体门控的离子通道有相加作用

General Anesthetics Have Additive Actions on Three Ligand Gated Ion Channels

Andrew Jenkins, PhD*, Ingrid A. Lobo, PhD{dagger}, Diane Gong, PharmD{dagger}, James R. Trudell, PhD{ddagger}, Ken Solt, MD§, R. Adron Harris, PhD{dagger}, and Edmond I. Eger, II, MD||

From the *Department of Anesthesiology, Emory University, Atlanta, Georgia; {dagger}Waggoner Center for Alcohol and Addiction Research, Section of Neurobiology and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas; {ddagger}Department of Anesthesiology, Stanford University, Stanford, California; §Department of Anesthesia and Critical Care, Massachusetts General Hospital and Department of Anesthesia, Harvard Medical School, Boston Massachusetts; and ||Department of Anesthesia and Perioperative Care, University of CA, San Francisco, California.

Anesth Analg 2008; 107:486-493

背景:本研究旨在确定成对的化合物包括全麻药,是否能够以一种协同的方式同时调制受体功能,以此来证明蛋白内存在多处麻醉药结合部位。

方法:通过使用标准的电生理方法,我们测定了包括苯、异氟烷(ISO)、氟烷(HAL)、氯仿、氟硝西泮、锌以及戊巴比妥至少一种药物以上复合对以下至少一种配体门控离子通道的作用:N-甲基-d-天冬氨酸受体、甘氨酸受体以及{gamma}-氨基丁酸A型受体。

结果:所有药物-药物-受体的结合都被发现呈相加而非协同性调制作用。ISO+苯呈累加性地抑制N-甲基-d-天冬氨酸受体功能。ISO+HAL和ISO+锌一样,呈累加性地增强甘氨酸受体功能。ISO+HAL和以下组合(HAL+氯仿、戊巴比妥+ISO、氟硝西泮+ISO)一样,呈累加性地增强{gamma}-氨基丁酸A型受体功能。

结论:同时发生的全麻药对配体门控离子通道的变构调制作用完全是相加性的。而成对的全麻药协同性地产生全身麻醉作用,必然基于较单个受体更为复杂的系统。

(黄施伟 译,马皓琳 李士通 校)

 

BACKGROUND: The purpose of this study was to determine whether pairs of compounds, including general anesthetics, could simultaneously modulate receptor function in a synergistic manner, thus demonstrating the existence of multiple intraprotein anesthetic binding sites.

METHODS: Using standard electrophysiologic methods, we measured the effects of at least one combination of benzene, isoflurane (ISO), halothane (HAL), chloroform, flunitrazepam, zinc, and pentobarbital on at least one of the following ligand gated ion channels: N-methyl-d-aspartate receptors, glycine receptors and {gamma}-aminobutyric acid type A receptors.

RESULTS: All drug-drug-receptor combinations were found to exhibit additive, not synergistic modulation. ISO with benzene additively depressed N-methyl-d-aspartate receptors function. ISO with HAL additively enhanced glycine receptors function, as did ISO with zinc. ISO with HAL additively enhanced {gamma}-aminobutyric acid type A receptors function as did all of the following: HAL with chloroform, pentobarbital with ISO, and flunitrazepam with ISO.

CONCLUSION: The simultaneous allosteric modulation of ligand gated ion channels by general anesthetics is entirely additive. Where pairs of general anesthetic drugs interact synergistically to produce general anesthesia, they must do so on systems more complex than a single receptor.



成人肌肉乙酰胆碱受体的成对竞争性拮抗剂之间的协同作用

Synergy Between Pairs of Competitive Antagonists at Adult Human Muscle Acetylcholine Receptors

Man Liu, PhD, and James P. Dilger, PhD

From the Department of Anesthesiology, Stony Brook University, Stony Brook, New York.

Anesth Analg 2008; 107:525-533

背景:临床上已经研究发现某些特定成对的烟碱乙酰胆碱受体(nAChR)竞争性拮抗剂的神经肌肉阻滞的协同作用。协同作用的机制还没有阐明。我们验证了这一假说,即协同作用源于拮抗剂在成人nAChR的两个配体结合位点的不同的选择性。

方法:我们在BOSC23细胞中表达了nAChR。在同时应用或无拮抗剂的情况下,我们在膜外面向外式膜片应用了乙酰胆碱,并且在室温下测量了可见电流。我们测定了(+)-筒箭毒碱、甲筒箭毒、哌库溴铵、维库溴铵、顺式阿曲库铵、罗库溴铵和阿曲库铵的IC90。对于两种拮抗剂的15种组合,我们测定了在第二种拮抗剂的IC70存在的情况下某种拮抗剂的IC90。我们绘制了90%抑制时的等效线图。对于单一的拮抗剂,我们测定了包括{epsilon}{delta}亚单元中的变异在内的受体抑制作用来确定位点选择性。

结果:两对拮抗剂,甲筒箭毒和顺式阿曲库铵以及顺式阿曲库铵和阿曲库铵呈相加作用。10种组合,包括(+)-筒箭毒碱和哌库溴铵以及哌库溴铵和维库溴铵,具有高度的协同性,以至于这种组合比期望的相加作用强2-3倍。3种组合比期望的相加作用强1.5-1.6倍。(+)-筒箭毒碱和甲筒箭毒的抑制作用仅对{epsilon}亚单元的突变敏感。维库溴铵仅受{delta}亚单元的突变的影响。其它拮抗剂的抑制作用可以被任一亚单元的突变所减低。

结论:很多拮抗剂的组合呈现出了对成人nAChR的协同作用。在结构上相似和不相似的拮抗剂观察到了协同作用。协同作用的程度并不总是与测定的突变位点特异性良好地相关。在某些,但不是全部的例子中,受体水平的协同作用与临床测定的协同作用相关。我们得出结论,肌肉松弛剂的协同作用的部分原因是与成人nAChR的直接相互作用。

(黄丽娜 译 马皓琳 李士通 校)

BACKGROUND: Synergistic neuromuscular blocking effects have been observed clinically with certain pairs of nicotinic acetylcholine receptor (nAChR) competitive antagonists. The mechanism for synergy has not been elucidated. We tested the hypothesis that synergy arises from a differential selectivity of antagonists for the two ligand binding sites on adult human nAChR.

METHODS: We expressed nAChR in BOSC23 cells. We applied ACh with or without antagonists to outside-out patches and measured macroscopic currents at room temperature. We determined the IC90 for (+)-tubocurarine, metocurine, pancuronium, vecuronium, cisatracurium, rocuronium, and atracurium. For 15 combinations of two antagonists, we determined the IC90 for one antagonist in the presence of the IC70 of a second antagonist. We constructed isobolograms for 90% inhibition. For single antagonists, we measured inhibition of receptors containing mutations in the {epsilon}- and {delta}-subunits to determine site selectivity.

RESULTS: Two pairs of antagonists, metocurine+cisatracurium and cisatracurium+ atracurium exhibited additive inhibition. Ten combinations, including (+)-tubocurarine+ pancuronium and pancuronium+vecuronium, were highly synergistic such that the combination was two to three times more effective than expected for additivity. Three combinations were 1.5–1.6 times more effective than expected for additivity. Inhibition by (+)-tubocurarine and metocurine was sensitive to mutations in the {epsilon}-subunit only. Vecuronium was affected by the {delta}-subunit mutation only. Inhibition by other antagonists was decreased by mutations in either subunit.

CONCLUSIONS: Many combinations of antagonists exhibited synergistic effects on adult human nAChR. Synergy was observed with structurally similar and dissimilar antagonists. The degree of synergy did not always correlate well with site specificity assayed with mutants. In some, but not all cases, the synergy at the receptor level correlated with clinical determinations of synergy. We conclude that the synergistic actions of muscle relaxants can be partially explained by direct interactions with adult human nAChR.



听觉诱发电位的卡嗒声对双频谱指数和熵的影响

The Effects of Auditory Evoked Potential Click Sounds on Bispectral Index and Entropy

 

Tomoki Nishiyama, MD, PhD

From the Department of Anesthesiology, The University of Tokyo, Tokyo, Japan.

Anesth Analg 2008; 107:545-548

背景:听觉诱发电位(AEP)的卡嗒声对脑电图指数和双频谱指数(BIS)会产生一定的影响,但是很多研究都测量了同时产生的指数却没有涉及这种影响。在本次研究中我监测了这种AEP的卡嗒声对BIS以及对熵监护仪测得的反应熵(RE)和状态熵(SE)的影响。

方法:四十位年龄在40—70岁之间择期在脊麻下行下肢手术的病人,用药为0.5%的布比卡因或丁卡因。病人镇静用1mg咪达唑仑,随后丙泊酚输注,开始速度1 mg · kg–1 · h–1。控制输注丙泊酚以使BIS或SE在80、60或40保持几分钟,然后给予65分贝的AEP卡嗒声60秒。卡嗒声停止后持续60 秒观察BIS、RE和SE的变化。

结果:在卡嗒声过程中BIS、RE和SE值显著增加。当BIS或SE值为60时这种增强作用持续时间最长。

结论:在脊麻时丙泊酚输注产生的不同程度的镇静过程中,AEP的卡嗒声可以一过性增强同时测定的BIS、RE和SE。因此,当AEP和这些监测指标同时应用于一个病人时,前者的卡嗒声对这些指标的影响必须要加以考虑。

(姜旭晖译,马皓琳 李士通校)

BACKGROUND: The click sounds of auditory evoked potentials (AEP) might have some effect on electroencephalogram indices and Bispectral Index (BIS) but many studies, unconcerned about this effect, have measured both indices simultaneously. In this study, I examined the effects, of AEP click sounds on the BIS, and also on the response entropy (RE) and state entropy (SE) of the entropy monitor.

METHODS: Forty patients aged 40–70 yr and scheduled for surgery of lower extremities under spinal anesthesia were anesthetized with 0.5% bupivacaine or tetracaine. Patients were sedated with midazolam 1 mg followed by propofol infusion started at 1 mg · kg–1 · h–1. Propofol infusion was controlled to keep BIS or SE at 80, 60, or 40 for several minutes, and then click sounds (65 dB) of the AEP were given for 60 s. The changes in BIS, RE, and SE were observed continuously for 60 s after the click sounds had stopped.

RESULTS: BIS, SE, and RE significantly increased during the click sounds. The longest duration of increase was at BIS or SE 60.

CONCLUSION: AEP monitor click sounds transiently increased the simultaneously measured BIS, RE, and SE during different levels of sedation by propofol infusion during spinal anesthesia. Therefore, the effects of the click sounds should be considered when these monitors are used simultaneously in the same patient.



死后的生命:围术期灾祸的后果

Life After Death: The Aftermath of Perioperative Catastrophes

Farnaz M. Gazoni, MD, Marcel E. Durieux, MD, PhD, and Lynda Wells, MD

From the Department of Anesthesiology, University of Virginia Health System, Charlottesville, Virginia.

Anesth Analg 2008; 107:591-600

大多数麻醉医师在其职业生涯中,会经历围术期患者死亡或较大的围术期灾祸。然而,麻醉训练没能使个人准备好处理此类应激事件的后果。多重调查显示:病人的死亡会对高达75%的有关卫生保健提供者产生较大的情绪影响,无论死亡是否为意料中或患者是否和医生熟识。心理上的复原通常需要数周或数月,并且,因缺乏情绪和专业支持而受阻碍。数据表明:大多数麻醉医生会青睐更正式的支持结构,包括从临床工作休息的选择权。即使围术期灾祸后专业功能的正式评估还未进行,英国和爱尔兰麻醉医师协会指定了推荐多级支持的指南,而在麻醉病人安全基础网站上的可用的“不利事件记录”提供了一系列步骤,以使患者损伤降到最低并在发生不良麻醉事件后鉴定其原因。在此类事件发生后未能妥善处理的负面后果同样对个人和卫生保健系统有重要意义。围术期灾祸对于提供者和卫生系统的短期和长期影响的更进一步研究是必要的。另外,如何处理围术期灾祸后果的教育和正式支持结构应当提供给各水平训练中的行医者。

(唐李隽    马皓琳  李士通 校)

Most anesthesiologists will experience the perioperative death of a patient or a major perioperative catastrophe in the course of their careers. Anesthesia training, however, does not prepare individuals to handle the aftermath of such a stressful event. Multiple surveys have shown that the death of a patient has a major emotional impact on up to 75% of health care providers involved, regardless of whether the death was expected or whether the patient was well known to the practitioner. Psychological recovery often takes weeks or months and is hampered by lack of emotional and professional support. Data indicate that the majority of anesthesiologists would prefer a more formal support structure, including the option to take time off from clinical work. Although a formal assessment of professional functioning after a perioperative catastrophe has not been done, the Association of Anaesthetists of Great Britain and Ireland instituted guidelines recommending support at multiple levels, and the "Adverse Event Protocol" available on the Anesthesia Patient Safety Foundation website provides a suggested series of steps to minimize patient injury and identify the cause of an adverse anesthesia event after it occurs. The negative consequences of failure to cope well after these events are significant to individuals and health care systems alike. Further study into the short-term and long-term impact of perioperative catastrophes on providers and health systems is needed. Additionally, education on how to handle the aftermath of perioperative catastrophes and formal support structures should be provided to practitioners at all levels of training.



阴部神经阻滞用于会阴切开术后疼痛缓解的随机对照研究

A Randomized Controlled Trial of Pudendal Nerve Block for Pain Relief After Episiotomy

 

Younès Aissaoui, MD*{dagger}, Rémi Bruyère, MD*, Hassan Mustapha, MD{ddagger}, Dominique Bry, MD*, Noureddine Drissi Kamili, MD, PhD{dagger}, and Chantal Miller, MD*

From the *Département d’Anesthésiologie, Centre Hospitalier d’Auxerre, France; {dagger}Département d’Anesthésie Réanimation et Urgences, Hôpital Militaire d’Instruction des Armées Mohammed V, Faculté de Médecine et de Pharmacie, Université Mohamed V Souissi, Rabat, Morocco; and {ddagger}Département de Gynécologie Obstétrique. Centre Hospitalier d’Auxerre. France.

Anesth Analg 2008; 107:625-629

背景:分娩过程中的会阴切开术或会阴撕裂引起产后期的显著疼痛。我们设计了这项随机双盲对照试验以研究神经刺激器引导下单侧会阴神经阻滞对会阴切开术后疼痛的缓解效果。

方法:40位阴道分娩过程中需要会阴正中旁切开的产妇随机分为两组:在会阴切开修补后用15mL的7.5mg/mL罗哌卡因(试验组)或生理盐水(对照组)行会阴神经阻滞。用会阴切开术后3、6、12、24和48 h时静息状态及活动(步行和坐)过程中的VAS评分来评价会阴切开的疼痛。难以忍受的疼痛(VAS>30 mm)则用每12h 700mg尼氟酸栓剂予以治疗。主要结果变量为会阴切开后48h内静息及活动时的疼痛评分。

结果:两组间人口统计学和产科特征方面均无差异。所有病人都成功完成了会阴神经刺激。试验组患者产后3、6、12、24和48 h时静息状态时的疼痛评分显著低于对照组(P < 0.05),在坐和步行时同样也获得了更好的镇痛效果。试验组和对照组分别有3位(15%)和17位(85%)病人需要额外镇痛治疗(P < 0.001)。

结论:此项研究显示用7.5mg/mL罗哌卡因行神经刺激器引导下的单侧会阴神经阻滞可以减弱会阴切开术后初始48h内的疼痛,并减少额外镇痛药的需要量。

(黄佳佳译,马皓琳 李士通校)

BACKGROUND: Pain from episiotomy or perineal tears during childbirth is associated with significant pain in the postpartum period. We performed this randomized, double-blind, controlled trial to investigate the efficacy of nerve stimulator-guided unilateral pudendal nerve block for pain relief after episiotomy.

METHODS: Forty women who gave birth vaginally with mediolateral episiotomy were randomized to receive pudendal nerve block with 15 mL of either ropivacaine 7.5 mg/mL (pudendal group) or normal saline (control group) after repair of the episiotomy. Episiotomy pain was assessed with a visual analog scale at rest at 3, 6, 12, 24, and 48 h postepisiotomy and during activities (walking and sitting). Breakthrough pain (visual analog scale >30 mm) was treated with niflumic acid suppositories 700 mg every 12 h. The primary outcome variables were pain scores at rest and during activities over 48 h postpartum.

RESULTS: Demographic and obstetric characteristics were not different between groups. Successful pudendal nerve stimulation was achieved in all patients. Patients in the pudendal group reported significantly lower pain scores at rest than those in the control group at 3, 6, 12, 24, and 48 h after delivery (P < 0.05). They also reported better analgesia while sitting and walking (P < 0.05). Additional analgesia was required by three patients (15%) in the pudendal group versus 17 patients (85%) in the placebo group (P < 0.001).

CONCLUSION: This study demonstrates that nerve stimulator-guided unilateral pudendal nerve block with ropivacaine 7.5 mg/mL is associated with decreased pain and need for additional analgesics during the first 48 h postepisiotomy.



右美托咪定静脉给药减少大鼠颅内高压引起的肺通透性

Intravenous Dexmedetomidine Decreases Lung Permeability Induced by Intracranial Hypertension in Rats

Motoi Kumagai, MD, Takashi Horiguchi, MD, Toshiaki Nishikawa, MD, Yoko Masaki, PhD, and Yoshitugu Tobe, BA

From the Department of Anesthesia and Intensive Care, Akita University School of Medicine, Akita, Japan.

Anesth Analg 2008; 107:643-647

背景:脑池内右美托咪定(DEX)减少颅内高压大鼠的心功能不全。然而,在颅内高压期间右美托咪定静脉给药对心功能和肺通透性方面的影响还未被评估过。我们假设右美托咪定静脉给药能减少大鼠颅内高压引起的血流动力学改变和肺通透性,并进行测试。

方法:氟烷麻醉并机械通气的大鼠分成4组。其中两组置入硬膜下带气囊的导管,充气60s以产生颅内高压。颅内高压前和后30min行动脉血气分析。平均动脉压、心率、颅内压持续监测30min。Dex组(n=8)静脉给右美托咪定首量80 µg/kg,继而6 µg · kg–1 · min–1(40 µg/mL)持续10 min,对照组(n=8)静脉给生理盐水首量2 mL/kg,继而0.15 mL · kg–1 · min–1持续 10 min。非颅内高压下施行手术,分为给右美托咪定(伪装-Dex组,n=5)和不给右美托咪定(伪装-对照, n = 5)。所有组用伊文思蓝染色渗出技术测量肺通透性。处死前2h给予伊文思蓝染料20 mg/kg,并用双波长分光光度分析技术量化血浆和肺组织中的伊文思蓝。

结果:各组间基础动脉压、心率、Pao2 均无显著性差异。对照组中,颅内高压短暂地增加平均动脉压和心率,随即迅速下降进入平台期。在Dex组,平均动脉压短暂升高,然后迅速降至基线,然而颅内高压时心率并未变化。颅内高压后Dex组Pao2比对照组高[138 (127–169)比78 (59–124) mm Hg, 中位数 (范围), P < 0.01]。肺通透性指数Dex组比对照组低[430 (182–450)比570 (427–1170), P < 0.01]。但伪装-Dex组比伪装-对照组高[25 (24–35)比6 (4–7), P < 0.01]。

结论:预防性静脉给予右美托咪定能减少大鼠颅内高压引起的肺通透性和血流动力学变化。

(朱 慧译 马皓琳 李士通校)

BACKGROUND: Intracisternal dexmedetomidine (Dex) attenuates cardiac dysfunction in rats with intracranial hypertension (ICH). However, the effects of IV Dex on cardiac function and lung permeability during ICH have not been evaluated. We tested the hypothesis that IV Dex attenuates hemodynamic changes and decreases lung permeability induced by ICH in rats.

METHODS: Halothane-anesthetized and mechanically ventilated rats were divided into four groups. In two groups, a subdural balloon catheter was inflated for 60 s to produce ICH. Arterial blood gas analysis was performed before and 30 min after ICH. Mean arterial blood pressure, heart rate (HR) and intracranial pressure were monitored for 30 min. The Dex group (n = 8) received IV Dex 80 µg/kg, followed by 6 µg · kg–1 · min–1 (40 µg/mL) for 10 min and the control group (n = 8) received IV saline 2 mL/kg, followed by at 0.15 mL · kg–1 · min–1 for 10 min. Surgery was performed without ICH with Dex (Sham-Dex group, n = 5) and without Dex (Sham-control, n = 5). In all groups, pulmonary permeability was measured using a modification of the Evans blue dye extravasation technique. IV Evans blue dye 20 mg/kg was administered 2 h before being killed and Evans blue dye in plasma and lung tissue was quantified by dual-wavelength spectrophotometric analysis.

RESULTS: There were no significant differences in basal arterial blood pressure, HR, and Pao2 among groups. In the control group, ICH resulted in transient increases in mean arterial blood pressure and HR, followed by a rapid decline and a plateau. In the Dex group, mean arterial blood pressure showed a transient increase and subsequent, rapid decrease to baseline, whereas HR did not change during ICH. Pao2 was higher in the Dex group than in the control group after ICH [138 (127–169) vs 78 (59–124) mm Hg, median (range), P < 0.01]. The pulmonary permeability index was lower in the Dex group than the control group [430 (182–450) vs 570 (427–1170), P < 0.01]. It was however, higher in the Sham-Dex group than the Sham-Control group [25 (24–35) vs 6 (4–7), P < 0.01].

CONCLUSIONS: Prophylactic IV Dex decreases lung permeability as well as hemodynamic changes induced by ICH in rats.



在特别1点上的针压法对插针主观和自主反应的影响

The Effect of Acupressure at the Extra 1 Point on Subjective and Autonomic Responses to Needle Insertion

Young-Chang P. Arai, MD*, Takahiro Ushida, MD*, Tomoaki Osuga, MD*, Takako Matsubara, PT*, Kahori Oshima{dagger}, Kana Kawaguchi{dagger}, Chiaki Kuwabara{dagger}, Sigeya Nakao{dagger}, Atsushi Hara{dagger}, Chihiro Furuta{dagger}, Erina Aida{dagger}, Shugyoku Ra{dagger}, Yui Takagi{dagger}, and Kyoko Watakabe{dagger}

From the *Multidisciplinary Pain Center, and {dagger}Society for Chinese and Kampo Medicine, Aichi Medical University, Aichi, Japan.

Anesth Analg 2008; 107:661-664

背景:术前镇静药可以减少创伤性麻醉操作的不适感。一些研究者表示在针刺特别1点上的针压法有镇静效果。我们研究在特别1点上的针压法是否能减轻插针的疼痛。

方法:我们用口述等级量表(VRS)疼痛分数和心率变异性(HRV)研究针压特别1点和假点对插针的效果。22例健康女性志愿者随机分为2组:特别1点组接受针压法针压特别1点,假点组接受针压假点。心电图记录开始后,27号针插入前臂皮肤。随后,在针压法过程中另一个针头插入另一前臂皮肤。

结果:针压特别1点明显减轻VRS,但针压在假点能增加VRS。针压特别1点明显减轻HRV对针刺的低频率/高频率反应。

结论:与假点比较,针压特别1点明显减轻插针疼痛。针压特别1点明显减少插针引起HRV低频率/高频率反应,表明减少交感神经系统活性。
(彭中美 译 马皓琳 李士通 校)

BACKGROUND: Premedication with sedatives can decrease the discomfort associated with invasive anesthetic procedures. Some researchers have shown that acupressure on the acupuncture extra 1 point is effective for sedation. We investigated whether acupressure on the extra 1 point could alleviate the pain of needle insertion.

METHODS: We investigated the effect of acupressure at the extra 1 point or a sham point on needle insertion using verbal rating scale (VRS) pain scores and heart rate variability (HRV). Twenty-two healthy female volunteers were randomly allocated to two groups: the extra 1 group received acupressure at the extra 1 point, and the sham group received acupressure at a sham point. After starting the electrocardiogram record, a 27-gauge needle was inserted into the skin of a forearm. Thereafter, another needle was inserted into the skin of the other forearm during acupressure.

RESULTS: Acupressure at the extra 1 point significantly reduced the VRS, but acupressure at the sham increased the VRS. Acupressure at the extra 1 significantly reduced the low frequency/high frequency ratio of HRV responding to needle insertion.

CONCLUSIONS: Acupressure at the extra 1 point significantly reduced needle insertion pain compared with acupressure at the sham point. Also, acupressure at the extra 1 point significantly reduced the low frequency/high frequency ratio of HRV responding to needle insertion, which implies a reduction in sympathetic nervous system activity.



调控钙内流可以调节大鼠背根神经节细胞膜兴奋性

Modulators of Calcium Influx Regulate Membrane Excitability in Rat Dorsal Root Ganglion Neurons

Philipp Lirk, MD*{dagger}, Mark Poroli, BS*, Marcel Rigaud, MD*, Andreas Fuchs, MD*{ddagger}, Patrick Fillip, MD*, Chun-Yuan Huang, PhD*, Marko Ljubkovic, MD*, Damir Sapunar, MD, PhD*§, and Quinn Hogan, MD*||

From the *Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin; {dagger}Department of Anesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria; {ddagger}Department of Intensive Care and Anesthesiology, Medical University of Graz, Graz, Austria; §University of Split Medical School, Split, Croatia; and ||Department of Anesthesiology, Milwaukee Veterans Administration Medical Center, Milwaukee, Wisconsin.

Anesth Analg 2008; 107:673-685

背景:神经元损伤导致的慢性神经性疼痛至今仍治疗困难,部分的原因是疼痛的细胞机制还不完全清楚。我们以往的研究显示,在啮齿类动物慢性神经性疼痛模型中,通过感觉神经元质膜的钙离子内流明显降低,但钙电流丧失对感觉神经功能的直接后果并未确定。因此我们研究了与钙内流消失相关的,神经损伤后神经膜性质变化,尤其是其兴奋性提高到哪种程度会导致慢性疼痛。

方法:从未受损伤的大鼠背根神经节上分离A型神经元,用细胞内微电极进行测定。在测定兴奋性和生物物理学常数时,改变记录条件以抑制或增强钙内流。

结果:降低外部浴槽中钙离子的浓度或用浴槽镉阻断钙内流,都使后超极化的持续时间和面积减少,并伴有动作电位初始的电流阈值的降低和持续去极化期间的反复触发增多。相反地,提高细胞外液钙离子浓度可以增强细胞后超极化,抑制反复触发。神经元超极化时膜电位下降,是由阳离子非选择性H电流造成的,降低浴槽中钙离子的浓度、用镉阻断钙电流,或细胞内钙离子的螯合剂都会抑制这个电流。使用钙内流亚型的选择性阻滞剂的研究提示,N-P/QL- R-型电流对细胞后超极化的产生均有影响,且阻断任何一种钙通道电流,均会降低动作电位的上升速度,延长动作电位时程,且(除了L型钙通道)降低引发动作电位的电流阈值。

结论:总之,我们的研究显示抑制内向钙电流会降低后超极化,减少超极化诱发的电压降低,提高感觉细胞元的兴奋性,重复这样的改变可能导致外周神经的损伤。这说明,损伤的感觉神经元中内向钙电流的降低会引发其功能障碍和过度兴奋,并可能导致神经性疼痛。

(张莹译  马皓琳 李士通校)

BACKGROUND: Chronic neuropathic pain resulting from neuronal damage remains difficult to treat, in part, because of incomplete understanding of underlying cellular mechanisms. We have previously shown that inward Ca2+ flux (ICa) across the sensory neuron plasmalemma is decreased in a rodent model of chronic neuropathic pain, but the direct consequence of this loss of ICa on function of the sensory neuron has not been defined. We therefore examined the extent to which altered membrane properties after nerve injury, especially increased excitability that may contribute to chronic pain, are attributable to diminished Ca2+ entry.

METHODS: Intracellular microelectrode measurements were obtained from A-type neurons of dorsal root ganglia excised from uninjured rats. Recording conditions were varied to suppress or promote ICa while biophysical variables and excitability were determined.

RESULTS: Both lowered external bath Ca2+ concentration and blockade of ICa with bath cadmium diminished the duration and area of the after-hyperpolarization (AHP), accompanied by decreased current threshold for action potential (AP) initiation and increased repetitive firing during sustained depolarization. Reciprocally, elevated bath Ca2+ increased the AHP and suppressed repetitive firing. Voltage sag during neuronal hyperpolarization, indicative of the cation-nonselective H-current, diminished with decreased bath Ca2+, cadmium application, or chelation of intracellular Ca2+. Additional recordings with selective blockers of ICa subtypes showed that N-, P/Q, L-, and R-type currents each contribute to generation of the AHP and that blockade of any of these, and the T-type current, slows the AP upstroke, prolongs the AP duration, and (except for L-type current) decreases the current threshold for AP initiation.

CONCLUSIONS: Taken together, our findings show that suppression of ICa decreases the AHP, reduces the hyperpolarization-induced voltage sag, and increases excitability in sensory neurons, replicating changes that follow peripheral nerve trauma. This suggests that the loss of ICa previously demonstrated in injured sensory neurons contributes to their dysfunction and hyperexcitability, and may lead to neuropathic pain.



不同浓度及容量的局麻药行连续腘窝坐骨神经阻滞的效果:一项双中心、随机、对照研究

The Effects of Varying Local Anesthetic Concentration and Volume on Continuous Popliteal Sciatic Nerve Blocks: A Dual-Center, Randomized, Controlled Study

Brian M. Ilfeld, MD, MS*, Vanessa J. Loland, MD*, J. C. Gerancher, MD{dagger}, Anupama N. Wadhwa, MD{ddagger}, Elizabeth M. Renehan, MSc, MD§, Daniel I. Sessler, MD||, Jonathan J. Shuster, PhD, Douglas W. Theriaque, MS#, Rosalita C. Maldonado, BS*, Edward R. Mariano, MD* For the PAINfRETM Investigators

From the *Department of Anesthesiology, University of California San Diego, San Diego, California; {dagger}Department of Anesthesiology, Wake Forest Medical Center; {ddagger}Department of Anesthesiology, University of Louisville, Louisville, Kentucky; §Department of Anesthesiology, University of Ottawa, Ottawa, Ontario, Canada; ||Department of Outcomes Research, The Cleveland Clinic, Cleveland, Ohio; ¶Department of Epidemiology and Health Policy Research, and #General Clinical Research Center, University of Florida, Gainesville, Florida.

Anesth Analg 2008; 107:701-707

背景:对于影响持续周围神经阻滞作用的主要因素是局麻药浓度还是仅为总药量,尚未明了。因此我们检验了这样一个检验假设,即使用不同浓度及速率、但总剂量相等的罗哌卡因行连续腘窝坐骨神经阻滞产生的效果相似。

方法:选择行中度疼痛的脚踝或脚踝远端部位矫形手术的患者,术前均从后腘窝径路插入神经周围导管到坐骨神经附近。术后将患者随机分成两组:术后第二天神经周围输注罗哌卡因0.2% (基础 8 mL/h,单次加量 4 mL)或 0.4% (基础4 mL/h, 单次加量2 mL)。因此,两组患者在每个小时内都接受了16 mg的罗哌卡因,通过病人自控的单次加量,每30分钟可能接受额外的8 mg。主要观察指标为从术后早晨开始的24小时内令人不快的肢体失去知觉的发生率。次要观察指标包括镇痛及病人满意度。

结果:与0.4%罗哌卡因组患者(n = 25)经历肢体无知觉0.6 (1.1) 〔均数(标准差)〕次比较,0.2%罗哌卡因组(n = 25)为1.8 (1.8)次,(估计的差异=1.2次95%可信区间,0.3–2.0次;P = 0.009)。相反,镇痛及满意度各组相似。

结论:对于连续腘窝坐骨神经阻滞,局麻药的浓度及容量影响其阻滞特性。使用较大容量相对低浓度的罗哌卡因时,患者肢体失去知觉更常见。因此在行连续腘窝坐骨神经阻滞时,使用相对高浓度较低容量的罗哌卡因似乎更可取。

(裘毅敏译,马皓琳、李士通校)

BACKGROUND: It remains unknown whether local anesthetic concentration, or simply total drug dose, is the primary determinant of continuous peripheral nerve block effects. We therefore tested the null hypothesis that providing different concentrations and rates of ropivacaine, but at equal total doses, produces comparable effects when used in a continuous sciatic nerve block in the popliteal fossa.

METHODS: Preoperatively, a perineural catheter was inserted adjacent to the sciatic nerve using a posterior popliteal approach in patients undergoing moderately painful orthopedic surgery at or distal to the ankle. Postoperatively, patients were randomly assigned to receive a perineural ropivacaine infusion of either 0.2% (basal 8 mL/h, bolus 4 mL) or 0.4% (basal 4 mL/h, bolus 2 mL) through the second postoperative day. Therefore, both groups received 16 mg of ropivacaine each hour with a possible addition of 8 mg every 30 min via a patient-controlled bolus dose. The primary end point was the incidence of an insensate limb, considered undesirable, during the 24-h period beginning the morning after surgery. Secondary end points included analgesia and patient satisfaction.

RESULTS: Patients given 0.2% ropivacaine (n = 25) experienced an insensate limb with a mean (sd) of 1.8 (1.8) times, compared with 0.6 (1.1) times for subjects receiving 0.4% ropivacaine (n = 25; estimated difference = 1.2 episodes, 95% confidence interval, 0.3–2.0 episodes; P = 0.009). In contrast, analgesia and satisfaction were similar in each group.

CONCLUSIONS: For continuous popliteal-sciatic nerve blocks, local anesthetic concentration and volume influence block characteristics. Insensate limbs were far more common with larger volumes of relatively dilute ropivacaine. During continuous sciatic nerve block in the popliteal fossa, a relatively concentrated solution in smaller volume thus appears preferable.