Table of Contents

August 2008

 

CARDIOVASCULAR ANESTHESIOLOGY:

兒童心臟手術人群中抗肝素-血小板因數4抗體的形成的發病率和意義

朱紫瑜 陳傑

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.

心臟手術中抑肽酶和氨甲環酸對血小板功能及術後失血的影響

胡豔譯   薛張剛校

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:

小兒吸入麻醉誘導期間不良行為依從的預測因數

潘錢玲 陳傑

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.

兒童肥大細胞增多症:常規麻醉管理一種複雜疾病

黃凝譯  薛張綱校

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:

預防性應用止吐藥物對嘔吐高危患者出院後噁心嘔吐發生率及恢復期生活功能性品質的影響:一項前瞻、隨機、雙盲比較兩種預防性止吐方案的試驗研究

邱郁薇 馬皓琳 李士通

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.

評價3種不同劑量的帕洛諾司瓊與安慰劑在術後72小時內防止術後噁心嘔吐的有效性和安全性的隨機雙盲研究

唐亮   馬皓琳 李士通

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.

一項隨機雙盲研究:評估三種不同劑量的帕洛諾司瓊與安慰劑對預防術後噁心嘔吐的有效性與安全性

陶穎瑩 陳傑

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.

當前止吐方案對高危病人影響的前瞻性研究

蔣宗明譯 薛張綱校

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.

病人危險因素與其術後早期以及後期發生嘔吐症狀的相關性分析

吳進   馬皓琳 李士通

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:

帕諾斯瓊在分子水準與5-羥色胺受體間獨特的相互作用

周姝婧 陳傑

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.

聯合吸入性麻醉藥之間對小鼠的最低肺泡濃度並不起到協同作用

劉沁譯 薛張綱校

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.

全麻藥對三種配體門控的離子通道有相加作用

黃施偉 譯,馬皓琳 李士通

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.

協同作用是普遍規律?關於產生催眠和肢體活動消失的麻醉藥相互作用的綜述

潘方立 陳傑

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.

麻醉藥相互協同作用:一項對麻醉機連接的理論分析

劉婷潔譯 薛張綱校

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.

成人肌肉乙醯膽鹼受體的成對競爭性拮抗劑之間的協同作用

黃麗娜 馬皓琳 李士通

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

Man Liu and James P. Dilger

Anesth Analg 2008 107: 525-533.

異丙酚對肝L02細胞的保護作用,啟動細胞外信號調節激酶通路減少因過氧化氫引起的細胞凋亡

懷曉蓉 陳傑

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:

使用神經導航儀時六種脈搏氧飽和度儀的表現

秦敏菊譯 薛張綱校

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.

聽覺誘發電位的卡嗒聲對雙頻譜指數和熵的影響

姜旭暉譯,馬皓琳 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:

冠狀動脈支架:第一部分 經皮冠狀動脈介入治療的進展

趙嫣紅 陳傑

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.

冠狀動脈支架:II 圍手術期思考與處理

施穎譯 薛張綱校

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.

死後的生命:圍術期災禍的後果

唐李雋    馬皓琳  李士通

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:

胸內血容指數可作為評估急性迴圈衰竭危重病人機體容量反應的一個指標:與中心靜脈壓的比較

葉樂 陳傑

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.

心臟手術後無創通氣結合肺複張療法的肺部效應

孫鵬飛譯 薛張綱校

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:

陰部神經阻滯用於會陰切開術後疼痛緩解的隨機對照研究

黃佳佳譯,馬皓琳 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:

隨機藥物抽檢減少麻醉住院醫師藥物依賴發生率:來自一個研究方案的初步結果

丁俊雲 陳傑

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:

關於在區域麻醉下接受頸動脈內膜剝脫術患者認知功能障礙的研究

夏俊明譯 薛張綱校

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.

右美托咪定靜脈給藥減少大鼠顱內高壓引起的肺通透性

慧譯 馬皓琳 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-甲基巴豆醯輔酶A羧化酶缺乏症病人的麻醉

杜唯佳 陳傑

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:

使用帕瑞考昔鈉20mg一天兩次的多日用藥法能減輕全髖置換術後的疼痛

宣麗真譯 薛張綱校

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.

在特別1點上的針壓法對插針主觀和自主反應的影響

彭中美 馬皓琳 李士通

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.

乳癌術後病人自控椎旁鎮痛的可行性:兩種方法的前瞻性、隨機雙盲研究的比較

舒慧剛 陳傑

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.

咪達唑侖在關節鏡膝蓋手術以後鎮痛的劑量-效果研究

章一靜譯 薛張綱校

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.

調控鈣內流可以調節大鼠背根神經節細胞膜興奮性

張瑩譯  馬皓琳 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.

長時使用嗎啡損害小鼠血管形成和內皮原細胞的活動

劉世文 陳傑

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.

鞘內注射可樂定可以抑制小鼠脊髓背側腳神經元的N-甲基-D-天門冬氨酸受體NR1磷酸化引起的神經性疼痛

陳珺珺譯 薛張綱校

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.

不同濃度及容量的局麻藥行連續膕窩坐骨神經阻滯的效果:一項雙中心、隨機、對照研究

裘毅敏譯,馬皓琳、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.

影響局麻藥在硬膜外麻醉神經阻滯平面的因素及腰段和胸段硬膜外麻醉的比較

張磊 陳傑

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.

心臟手術中抑肽酶和氨甲環酸對血小板功能及術後失血的影響

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:當前抗纖維蛋白溶解的藥物,包括抑肽酶和氨甲環酸被用於心臟手術,通過對血小板不同的作用來減少術後的出血及輸血需求。所以我們通過評估體外迴圈和心臟手術後的血小板功能來確定抑肽酶及氨甲環酸的作用。

方法:在一個隨機的前瞻性研究中,對50位擇期行體外迴圈心臟手術病人進行研究。25位接受高劑量的抑肽酶,25位接受高劑量的氨甲環酸。術前,體外迴圈後,術後3小時,24小時用改良的血栓彈性描記法和全血集合度測定來評價凝血及血小板功能。

結果:與術前相比,體外迴圈後兩組的凝血的功能均受到損害(P < 0.01)。與改良的血栓彈性描記法的測定結果不同,體外迴圈後,使用氨甲環酸的病人的凝血酶受體介導的集合度有明顯的下降(P < 0.05)。與使用氨甲環酸組相比,使用抑肽酶的患者的胸管引流量明顯減少(575 mL +/- 228 vs 1033 mL +/- 647, P < 0.05),術後的輸血需求明顯下降(P < 0.01)

結論:使用全血集合度測定血小板功能顯示抑肽酶和氨甲環酸能減少體外迴圈後最初24小時內的出血。

(胡豔譯   薛張剛校)

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.

 

 

兒童肥大細胞增多症:常規麻醉管理一種複雜疾病

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:兒童肥大細胞增多症包括一系列臨床變種,具有多器官系統內固有肥大細胞數目增多的特徵。肥大細胞在介導過敏反應方面起作用,肥大細胞增多症患者易發生有或無刺激的過敏反應發作。

方法:調查自1993年至2006年為診斷或外科手術接受麻醉的兒童肥大細胞增多症患者的圍麻醉期記錄,同時進行有關兒童肥大細胞增多症麻醉經驗的文獻回顧。

結果:行麻醉時平均年齡為3.2(年齡6個月-20)22名兒童肥大細胞增多症患者,29次為診斷或外科手術接受麻醉。此佇列中包括該病所有變種。大多數患者有皮膚潮紅,瘙癢,胃食管反流症和腹痛病史,一名患者有自發性過敏反應病史。不考慮該病的複雜性採用常規麻醉技術,整個圍術期經過並不複雜,且無嚴重不良事件。

結論:回顧兒童肥大細胞增多症的主要特點和它所涉及的麻醉及圍術期問題,並敍述此類兒科患者麻醉管理的實用方法。儘管很多麻醉中常規使用的藥物據報導可引起肥大細胞脫顆粒,但並無依據證實與常規麻醉技術的差異是有必要的。然而為處理可能發生的不良事件,建議應瞭解此病所涉及的麻醉問題並仔細準備。

(黃凝譯  薛張綱校)

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.

 

 

當前止吐方案對高危病人影響的前瞻性研究

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:該前瞻性、多中心、觀察研究中將評價高危病人術後噁心嘔吐(PONV)的發生率和持續時間,分析預防性和補救性止吐藥物的使用,總結止吐藥物使用指南對人群的有效性,其指南包括美國麻醉醫師協會(ASA)和美國圍麻醉期護理學會(ASPAN)指南。

方法:擬擇期行腹腔鏡手術或整形外科大手術的入選病人有下列兩個或兩個以上下列PONV危險因素:女性、PONV病史或運動暈動病、不吸煙。手術後第一個72h記錄下列指標:止吐藥物使用、嘔吐事件發生、噁心嚴重性和因PONV對正常功能的干擾。止吐完全有效(CR)為無嘔吐發生或無補救藥物使用,止吐完全控制為CR和無中-重度噁心。分析受試者的ASAASPAN指南藥物使用依從性對PONV發生率的影響。

結果:研究者中18-40%病人有術後嘔吐發生,其發生比例取決於使用止吐藥物的數量。補救藥物使用率為45%,其比例接近於先前報導的中-重度噁心發生率(47%)。因嘔吐症狀對生理功能干擾發生率為44%。使用3種及以上止吐藥物產生的總體止吐效果優於使用少於1種預防性藥物者。儘管受試者遵守ASA ASPAN使用指南,但CR率小於70%(ASA: 69%; ASPAN: 63%)PONV完全控制率為10%低於3天研究期間CR率。

結論:對PONV高危因素病人,預防性使用3種或3種以上止吐藥物對手術後病人72h內嘔吐發生能產生積極結果。儘管遵從各個學會推薦的PONV使用指南,高危病人術後嘔吐症狀及其對病人正常活動干擾發生率仍大於30%

(蔣宗明譯 薛張綱校)

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.

 

 

聯合吸入性麻醉藥之間對小鼠的最低肺泡濃度並不起到協同作用

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:我們假設有歧異效價[指一種對最低肺泡濃度(MAC)的作用小,而另一種作用大]的兩種吸入性麻醉藥對某一受體或通道可能有著協同作用。並且,這種可加性的偏差對我們關於麻醉藥物是在多位點來發揮麻醉效應的觀點也起到了支持作用。

方法:相應的,我們研究了11對有著歧異效價(一種對MAC的作用小,一種作用大)的麻醉藥物作用於某特一受體或通道時其MAC的可加性。所謂的“歧異作用”,我們通常是指在MAC上,那種對體內某特一受體或通道作用強的麻醉藥其激動或阻斷效應至少是較弱的那種的兩倍(而通常是更多)。這些受體或通道包括:TREK-1/TASK-3鉀通道、A{gamma}-氨基丁酸受體、甘氨酸受體、N-甲基右旋天冬氨酸受體和乙醯膽鹼受體。我們還研究了苯環丙烷的可加性,因為N-甲基右旋天冬氨酸的阻斷劑MK-801對於這些麻醉藥物的MAC值也有歧異效應。此外,我們還研究了包括笑氣在內的四組吸入性麻醉藥的配對,因為有文獻報導當笑氣與異氟醚合用時有次相加性(拮抗作用)的產生。

結果:除了有次相加性的笑氣和異氟醚間的組合之外,其他所有的配對都得到了一個根據可加性得出的其預計值10%以內的結果。

結論:有觀點認為,當遭遇有害刺激時,吸入性麻醉藥是通過作用于某單一位點來達到麻醉制動效果的,而我們的結果正也與這一觀點相一致。

(劉沁譯 薛張綱校)

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.

 

 

麻醉藥相互協同作用:一項對麻醉機連接的理論分析

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:吸入性麻醉藥假定作用於多種受體,在各方適度作用的疊加下產生固定的有害刺激。最近實驗研究結果有了吸入性麻醉藥相互影響的新發現。協同意味多方面的作用。這次嘗試,我們探究相反的:在一方面有無疊加作用?

方法:用大量的聚集反應方法探索一對同一受體結合位置的競爭配體。構建一個電路來研究藥物力量和不合理的濃度反映關係在有抑制物管理的連續電路中怎樣被放大,在平行電路中被增強。集合的抑制物和增強電路進入信號處理單元來研究信號處理單位強制施加的影響所產生的附加交互作用。最後,協同,疊加,和佔有部分受體之間的關係被探究來理解疊加後強制施加的影響。

結果:競爭性結合同一受體的藥物與有相似效應的受體必須一一被添加。受體被抑制物固定在連續的電路中。在平行電路中被擴大,增加顯著的藥物力量與不合理的濃度反映關係。當集合的抑制物和增強的電路被安排進信號處理單元,相互作用會疊加或協同。關鍵在於藥物濃度與影響效應和濃度與50%受體佔有之間的關係,kd效應被低的濃度調節更可能被疊加。相似的,如果麻醉藥效應出現在濃度在或超過50%受體被佔有時,吸入性麻醉藥在分離的地點作用不會顯示疊加的交互作用。然而,如果麻醉藥物效應出現在濃度非常低的受體被佔有時,疊加作用會在其他麻醉作用受體上出現。

結論:藥物在不同受體上的疊加作用只有在濃度依賴性藥物濃度低於50%受體被佔有時產生。

(劉婷潔譯 薛張綱校)

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.

 

 

使用神經導航儀時六種脈搏氧飽和度儀的表現

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:脈搏氧飽和度儀的使用已被公認是麻醉過程中的基本監護之一。然而,這種監護設備也很容易被多種外界干擾所影響。最近有看法指出,神經導航設備會影響脈搏氧飽和度儀的精確性。本次研究中,我們評估六種不同的脈搏氧飽和度儀在受到一種神經外科影像導航儀影響時的表現。另還將評估兩種簡單的遮罩措施的效果。

方法:本研究入選二十個健康、成年、不抽煙的志願者,在他們雙手手指上夾上六種不同的脈搏氧飽和度儀,評估其心率、動脈氧飽和度、信號品質的基線。開啟Brain Lab Vector Vision 神經導航系統儀後,記錄下其對信號品質、飽和度識別的影響。並使用兩種不同的遮罩方法:棉毯及鋁箔,分別重複測定記錄值。

結果:影像導航儀的啟動對信號品質及飽和度識別檢測帶來了有統計學意義的干擾。而這種干擾可在一定程度上被兩種遮罩方法所逆轉。六種不同品牌的脈搏氧飽和度儀的信號品質有統計學意義的差別(p<0.001);氧飽和度識別也有統計學意義的差別(p<0.001);對於遮罩方法的反應性也有統計學意義的差別(p<0.001)。由鋁箔遮罩的測試中,所有受試的探頭監測到的飽和度值幾乎沒有受到影響。

結論:神經導航儀的紅外線脈衝會影響到脈搏氧飽和度儀的監測。而將探頭用鋁箔遮罩能顯著地消除這種干擾。

(秦敏菊譯 薛張綱校)

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 (P0.001).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.

 

 

冠狀動脈支架:II 圍手術期思考與處理

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

 

裝有冠狀動脈支架的患者的圍手術期管理,是臨床醫生所需面對的關係到患者生命安全的要點之一。無論是裸金屬還是藥物洗脫支架,圍手術期支架血栓都是危及患者生命的嚴重併發症。非心臟手術似乎增加支架血栓、心肌梗死及死亡風險,特別是支架植入術後早期即接受手術的患者。術前停止雙抗血小板治療將進一步增加併發症發生可能。通常認為,除外出血風險顯著大於繼續的抗凝治療,阿司匹林應在整個圍手術期持續使用。我們建議局麻,因為術後是圍手術期支架血栓發生可能最大的階段。一旦發生支架血栓,24小時內患者應被送入心臟介入室,立即經皮冠狀動脈介入治療是治療圍手術期支架血栓的有效療法。本文最後提出了圍手術期裸金屬及藥物洗脫支架植入患者的不同處理建議。

(施穎譯 薛張綱校)

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.

 

 

心臟手術後無創通氣結合肺複張療法的肺部效應

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:該研究的目標是評估開放性心臟手術後無創通氣(NIV)結合或不結合肺複張療法(RM)的肺效應。

方法 :100名冠脈旁路術後的病人被隨機分為4組。1)術後機械通氣結合持續膨肺的RM (RM , n = 25) 2)手術結束拔管後第一天裏無創通氣每6小時給與半小時的RM (RM-NIV , n = 25) 3)拔管後NIV (NIV , n = 25) 4)控制組,由不接受NIVRM的病人組成(控制組, n = 25)。各組間比較肺功能測試,氧指數,和胸片下的肺膨脹不全的情況。

結果:機械通氣期間的RM和拔管後的RM比其他干涉提供了更高的脈氧飽和度。RM-NIV NIV組在研究最後的氧飽和度比控制組好。控制組術後肺膨脹不全評分(均數: 1) RM組高(1; P = 0.03), RM-NIV (0; P < 0.01),比NIV組高 (0; P < 0.01)NIV組在術後第二天的肺功能比其他組好,而術後第七天這一結果在各組之間差不多。

結論NIV結合RM在機械通氣期間和之後都提供更高的氧飽和度。NIV或結合RM. NIV 比控制組提供更低的肺膨脹不全評分和更好的早期肺功能測試結果,而是否在機械通氣期間,是否在加護病房和住院天數對此沒有顯著影響。心臟手術後採用NIV結合RM療法有助於預防肺膨脹不全和低氧血症。

(孫鵬飛譯 薛張綱校)

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.

 

 

關於在區域麻醉下接受頸動脈內膜剝脫術患者認知功能障礙的研究

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:既往研究發現,與對照組相比,在全身麻醉下接受頸動脈內膜剝脫術(CEA)的患者中約25%在術後1天到一個月內發生認知功能障礙。在本次研究中,我們假定,與接受鎮靜治療的對照組相比,在區域麻醉下接受CEA術的患者會在術後1天出現認知功能障礙。

方法:為驗證假設,我們招收60名患者加入前瞻性研究。在區域麻醉下行CEA術的41位患者接受頸深叢及淺叢神經阻滯。對照組由19位在鎮靜治療下接受冠狀動脈造影術或支架術的患者組成。為解決重複進行認知水準測驗而引起的“練習效果”問題,對照組是必不可少的。實驗組患者來源於紐約醫學研究中心,對照組患者來源於哥倫比亞長老會醫學研究中心。所有患者的認知水準經由一系列既經證實有效的神經心理學測驗評估。術後一天與術前相比的差異性表現由事件發生率和群組發生率來評價。

結果:術後一天,在區域麻醉下接受CEA術的患者中有24.4% 發生顯著的認知功能障礙,此處的“顯著”定義為比對照組的平均評分低兩個標準差以上。

結論:在區域麻醉下接受CEA術的患者有發生術後認知功能障礙的可能,其幾率與以往報導過的全麻下CEA術者沒有明顯差別。

(夏俊明譯 薛張綱校)
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.

                                                          

 

使用帕瑞考昔鈉20mg一天兩次的多日用藥法能減輕全髖置換術後的疼痛

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:這項多中心、多種劑量、隨機、雙盲、平行分組的研究比較了在全髖置換術後使用帕瑞考昔鈉(帕瑞考昔)的兩種給藥方案對照安慰劑組的止痛效果和安全性。

方法:在第一試驗日,490名患者在術後得到靜脈注射帕瑞考昔40mg的起始負荷劑量,隨後對490名患者中的484名再次使用帕瑞考昔20mg。第二試驗日隨機挑選479名患者進行雙盲治療:帕瑞考昔20mg bid組(n=159),使用安慰劑後使用帕瑞考昔20mg qd組(n=159)和安慰劑組(n=161)。

結果:帕瑞考昔20mg bid治療組的病人在第25天比安慰劑組病人顯示明顯低的24小時總疼痛強度(SPI-24)評分和改善的病人的藥物治療研究的全球評價(PGESM)等級(P<0.05)。帕瑞考昔20mg qd治療組的病人在第34天的SPI-24評分比安慰劑組顯著的低P<0.05PGESM評級在第5天比安慰劑組改善。除了發熱、嘔吐和注意力不集中在安慰劑組中較其他帕瑞考昔治療組更為常見(P<0.05),不良事件的發生率在所有治療組中相似。

結論:帕瑞考昔20mg一天一次或兩次的多日給藥法在全髖置換術後是有效和普遍耐受的。

(宣麗真譯 薛張綱校)

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.

 

 

咪達唑侖在關節鏡膝蓋手術以後鎮痛的劑量-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 各種各樣的鎮痛藥技術被用於在關節鏡膝蓋手術以後處理手術後痛苦。 關節腔內使用咪達唑侖的鎮痛作用和中樞神經內使用咪達唑侖的鎮痛作用相似。

方法: 60ASA III級的接受關節鏡檢查的患者實行全身麻醉,並隨機化接受關節腔內注射咪達唑侖50 µg/kg75 µg/kg或者等滲鹽。我們通過以下幾個方面評估鎮痛藥的效果:直觀鎮痛評分、首次要求鎮痛的時間、累計鎮痛藥的消耗。患者總共觀察48 h

結果:相比於等滲鹽,早期關節腔內注射咪達唑侖可以明顯降低直觀鎮痛評分。兩藥量都可以延長首次要求鎮痛的時間(4.7 4.6 vs 0.7 h)。使用兩種劑量的藥物對於累計鎮痛藥的消耗方面沒有統計學的差異。

結論: 我們認為,在關節鏡手術後,相比於安慰劑,關節腔內注射咪達唑侖可以減輕術後疼痛, 然而這種鎮痛作用鎮痛是相對短期的。

(章一靜譯 薛張綱校)

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

 

 

鞘內注射可樂定可以抑制小鼠脊髓背側腳神經元的N-甲基-D-天門冬氨酸受體NR1磷酸化引起的神經性疼痛

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:鞘內注射α受體拮抗劑可樂定有鎮痛的效果。儘管有一些關於可樂定相關的鎮痛機制假設,但是作為主要抗傷害性刺激機制的N-甲基-D-天門冬氨酸(NMDA)受體,其與可樂定作用的關係尚沒有很多研究。我們設計了這個試驗來研究可樂定或者其他鎮痛藥物是否可以影響小鼠脊髓NMDA受體,從而緩解慢性縮窄性損傷(CCI)引起的神經病症狀。

方法:單側CCI的小鼠分別鞘內注射可樂定(1520ug/小鼠),[d- 丙氨酸2, N甲基煙醯胺-苯丙氨酸4, 甘氨酸-ol5]-腦啡肽 (DAMGO, µ 阿片受體拮抗劑, 1 µg/小鼠),加巴噴丁(抗驚厥藥物,100 µg/小鼠)。注射之後,我們測定了小鼠對熱或機械刺激的痛覺反應,並使用免疫組化評估脊髓磷酸化的NMDA受體亞單位1pNR1)的表達。

結果:CCI手術後兩周,小鼠表現出對熱和機械刺激的異常痛覺敏感,脊髓背側腳的pNR1神經元的表達也增加。鞘內注射可樂定(20 µg/小鼠)DAMGO和加巴噴丁可以潛在降低機械或熱刺激引起的痛覺反應。重要的是,鞘內注射可樂定,但是不注射DAMGO和加巴噴丁,在注射後30min可以劑量依賴性的降低CCI導致的脊髓背側腳的pNR1的表達。另外,可樂定可以抑制CCI導致的脊髓背側角NR1磷酸化,但是在注射可樂定之前10min,鞘內注射α-2受體拮抗劑咪唑克生(40 µg/小鼠),可以完全逆轉其對抗痛覺過敏的效果。

結論:我們的資料顯示,鞘內注射可樂定的對抗痛覺過敏的作用與降低脊髓NMDA受體磷酸化有關,並提示可樂定的潛在的作用機制。

(陳珺珺譯 薛張綱校)

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.

 

兒童心臟手術人群中抗肝素-血小板因數4抗體的形成的發病率和意義

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:兒童心臟手術人群中血清抗肝素-血小板因數4抗體的發病率和意義仍未闡明。作者前瞻性研究以下兩種群體中血清轉化的發生率:首次施行心臟手術的新生兒以及有普通肝素使用史的再次心臟手術兒童。

方法:研究連續135名患者:新生兒組:60名新生兒,第一次心臟外科手術;再次手術組:75名,再次心臟手術者。分別對術前和術後5天及10天的血液樣本進行酶聯免疫吸附試驗,從而確認是否有PF4免疫球蛋白GAM抗體。

結果:兩組患者術前均未檢測到抗肝素/抗肝素-血小板因數4抗體。在術後5天新生兒組1名患者(1.7%)檢測到抗體;再次手術組12名患者(16%)檢測到抗體;組間差異顯著(P=0.006)。術後10天,新生兒組1名患者(1.7%)檢測到抗體;再次手術組39名患者(52%)檢測到抗體(P<0.001)。再次手術組的患者術後10天的血清與普通肝素使用史間有良好的相關性(P=0.003)。在任一新生兒組的患者中,未發現肝素誘導的血小板減少症(HIT)。再次手術組中一名患者(1.3%)發生了血清轉化並發生了HIT,但沒有發生血栓或者皮膚病損。

結論:HIT在兒童心臟手術患者中鮮有發生。在再次手術的兒童中,術後10天的抗肝素-血小板因數4抗體血清轉化的發病率大約為50%,在成人心臟外科手術患者中有相似的發現。年齡和普通肝素使用史與此血清轉化率有關。相反,新生兒初次手術組中血清轉化率比較低。

(朱紫瑜 陳傑 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.

 

小兒吸入麻醉誘導期間不良行為依從的預測因數

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:術前確定小兒吸入麻醉誘導期間有情緒痛苦及不良行為依從有助於進行定向干預以減少痛苦,從而改善麻醉品質。本文作者探索了識別患者、操作、健康護理系統等因素預測誘導期間不良行為依從的方法。

方法:選擇861名發育正常的1-13歲,ASAI-III級,進行吸入麻醉誘導的小兒。所有的麻醉誘導在誘導室中由父母陪伴下完成。行為習慣通過ICC評估,即一種觀察量表,測定誘導期間對行為進行觀察所獲得的數值,ICC≥4認為行為順從性差。行為依從性通過一個多變數定向邏輯回歸模型取得,多變數模型特徵由c統計法評估。

結果21%小兒在麻醉誘導時出現不良行為依從。年齡小(<4y, p<0.001),術前準備時間短(p=0.004, 術前焦慮(修訂的耶魯術前焦慮標準>40p=0.016)等因素增加了不良行為依從可能性。先前的麻醉經歷增加了學齡兒童的可能性(p=0.046);這種影響在參加術前培訓的孩子中有所改善(p=0.018)。這些因素在有不良行為依從與良好的行為依從(ICC=0)(c統計=0.75)的孩子間有差異。

結論:不良行為依從的預測因數有年齡,先前的麻醉經歷,以及在術前門診進行的術前培訓,術前準備時間及焦慮程度等。包含這些因數的預測程式,有助於分辨能從行為或藥理干預受益的孩子以及不需要干預的低風險的孩子。

(潘錢玲 陳傑 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.

 

一項隨機雙盲研究:評估三種不同劑量的帕洛諾司瓊與安慰劑對預防術後噁心嘔吐的有效性與安全性

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:為了評估三種劑量的新型5-HT3受體阻滯劑---帕洛諾司瓊的有效性及安全性,作者進行這一隨機雙盲研究,觀察術後72小時的PONV(術後噁心嘔吐)發病率及嚴重程度。

方法:作者對574名門診腹部手術或腹腔鏡下行婦科手術病人,根據其性別、有無PONV史、有無運動病、是否吸煙分層。有≥2PONV危險因素的病人入組並在麻醉誘導前即刻隨機靜脈予以三種劑量(0.025mg0.05mg0.075mg)帕洛諾司瓊中一種或安慰劑。隨後觀察帕洛諾司瓊的主要療效指標(co-primary efficacy end-points)包括術後0-24小時、24-72小時兩個時段的完全緩解率(指無嘔吐及不需補救藥物,CR)。

結果:部分病人在第一個24小時出現與帕洛諾司瓊劑量相關的CR。而在術後0-24小時這一時段安慰劑及帕洛諾司瓊(0.075mg)的CR率分別為26%43%P=0.004),在術後24-72小時,安慰劑及帕洛諾司瓊(0.075mg)的CR率分別為41%49%P=0.188)。與安慰劑相比帕洛諾司瓊(0.075mg可以顯著降低嚴重噁心發生率(P=0.042)及減輕術後0-24小時內PONV對病人的影響(P=0.004)。

結論:帕洛諾司瓊(0.075mg)能顯著降低術後0-24小時內的CR率,減輕噁心程度,減少病人術後PONV的發生。

(陶穎瑩 陳傑 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.

 

帕諾斯瓊在分子水準與5-羥色胺受體間獨特的相互作用

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期臨床試驗中,與其他5-羥色胺受體拮抗劑相比,帕諾斯瓊被證實能更有效地預防急性、遲發性,及其它由化療所引發的噁心和嘔吐。帕諾斯瓊強大的臨床效力可能部分源於它有更長的半衰期,及其與受體間更大的親和力。然而,帕諾斯瓊的這些特性並不足以解釋它的藥效。作者試圖進一步闡明不同5-羥色胺受體間的差異,希望這有助於解釋臨床的觀察結果。

方法:作者用3H-帕諾斯瓊、3H-格拉鐘斯和3H-奧坦西隆進行受體位點飽和結合試驗,以獲得相應的Scatchard分析和Hill係數。通過診斷性平衡結合試驗和動力學解離試驗,評價帕諾斯瓊、格拉鐘斯和奧坦西隆與5-羥色胺受體間的相互競爭和變構作用。最後,比較了三種拮抗劑對受體功能的長期效應,通過檢測表達5-羥色胺受體的HEK293細胞內的鈣內流實現的。

結果:通過ScatchardHill曲線分析結合等溫線,作者發現單一雙分子結合的格拉鐘斯和奧坦西隆與帕諾斯瓊之間存在協同效應。平衡診斷試驗表明帕諾斯瓊對3H配體有不同的結合效應,這說明帕諾斯瓊是一種異構性拮抗劑,而格拉斯瓊和奧坦西隆是競爭性拮抗劑。通過測定解離速率發現,帕諾斯瓊是一種變構的效應物,它能夠加快格拉斯瓊和奧坦西隆與受體的解離速率。帕諾斯瓊與5-羥色胺受體間不同的結合模式影響受體功能的發揮。在這些試驗中,用每一種拮抗劑孵化細胞,然後使其無限稀釋和解離2.5小時。可以觀察到,在用格拉斯瓊或奧坦西隆孵化的細胞中出現了與未暴露於5-羥色胺受體的對照組細胞中相似的鈣離子內流;與其相反,在用帕諾斯瓊孵化的細胞中觀察到了強大的鈣內流抑制效應。

結論:帕諾斯瓊是一種異構性結合劑,當它與5-羥色胺受體結合時,產生協同效應。同時,帕諾斯瓊觸發的功能性效應的持續時間長於它與細胞表面受體的結合時間。它與受體的結合位點不同,及其導致的不同的受體功能可能與它獨特的臨床效益相關。作者認為,這是首次在分子水準探討帕諾斯瓊與5-羥色胺受體之間的相互作用,這也是它與其他5-羥色胺受體拮抗劑的截然不同之處。

(周姝婧 陳傑

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.

 

 協同作用是普遍規律?關於產生催眠和肢體活動消失的麻醉藥相互作用的綜述

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:藥物的相互作用可以揭示藥物作用的機制:相加作用提示作用於同一位點,協同作用提示作用於不同位點。筆者應用這一推理回顧了已出版的最終會引起催眠和肢體活動消失的麻醉藥物的相互作用。

方法:筆者搜索了Medline上所有的列有下列藥物相互作用的原稿:丙泊酚、依託咪酯、美索比妥、硫苯妥鈉、咪唑安定、地西泮、氯胺酮、右美托咪定,可樂定、嗎啡、芬太尼、舒芬太尼、阿芬太尼、瑞芬太尼、氟呱利多、甲氧氯普胺、利多卡因、氟烷、恩氟醚、異氟醚、七氟醚、地氟醚、N2O和氙氣,相互作用包括相加、協同、拮抗、等效。如果可能,資料將應用分數分析和回應面分析。

結果:在不同藥物種類之間大多數相互作用是協同作用。氯胺酮是個例外,其主要相互作用是相加或拮抗作用。吸入麻醉藥和靜脈麻醉藥之間主要為協同作用,但也有相加作用或在某些情況下可能是拮抗作用,如笑氣和異氟醚。

結論:除了氯胺酮,靜脈麻醉藥通常作用於不同位點產生協同作用,吸入麻醉藥通常和靜脈麻醉藥之間是協同作用,但吸入麻醉藥之間不呈協同作用。

(潘方立 陳傑 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.

 

異丙酚對肝L02細胞的保護作用,啟動細胞外信號調節激酶通路減少因過氧化氫引起的細胞凋亡

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:在一些器官中異丙酚可以通過抑制缺血/再灌注所造成的損傷來保護細胞,但很少有關於它對肝上皮細胞作用的報告。作者研究了經異丙酚預處理的肝L02細胞在過氧化氫(H2O2)氧化應激情況下的效應,判斷在這個過程中是否存在細胞外信號調節激酶(ERK)通路。

方法:預處理或未預處理過的人類肝L02細胞暴露在H2O2中,根據TUNEL測定、半胱天冬酶3、多形核白細胞ADP-核糖聚合酶(PARP)的分裂,來評估細胞凋亡的變化。ERK1/2的啟動,絲裂原啟動蛋白激酶//ERL激酶1/2(MEK1/2)由西方墨蹟分析法量度。Bcl-2,Bcl-xL,Bad,BaxmRNA的表達用即時定量的逆轉錄酶聚合酶鏈反應來定量。

結果:異丙酚預處理可以減少由過氧化氫引起的肝內L02細胞凋亡、半胱天冬酶3PARP分裂的總數。肝L02細胞單獨用異丙酚(0.01-0.3mM)處理,ERKMEK的劑量依存性啟動的最小劑量,這種啟動可以在0.5h內被檢測到, 4h時到達下限<50%。特異抑制劑PD98059可完全抑制ERK的啟動並加重細胞凋亡的程度。異丙酚處理可抑制凋亡基因BadBax mRNA表達,且這種反應可部分被PD98059逆轉。

結論:這些研究結果表明,異丙酚對過氧化氫應激的肝L02細胞的具有保護作用,部分通過啟動MEK-ERK通路,從而進一步抑制BadBax的表達來實現的。

(懷曉蓉 陳傑 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.

 

冠狀動脈支架:第一部分 經皮冠狀動脈介入治療的進展

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.

 

在過去的三十年,隨著經皮腔內冠狀動脈血管成形術和經皮腔內斑塊旋切術,裸金屬支架和藥物洗脫支架的快速發展,心臟介入技術在冠狀動脈性心臟病的治療方面有了顯著進展。裸金屬支架(BMS)通過血管成形術維持血管腔的直徑防止其塌陷。然而,裸金屬支架會引起內膜增生從而產生支架內再狹窄,超過20%的病人需要再次行介入治療,通過藥物洗脫支架(DES)(包括西羅莫斯洗脫支架和紫杉醇洗脫支架)抑制血管內皮增生來防止再狹窄。然而,藥物洗脫支架對血管內皮細胞生長的延遲在某種程度上會引起支架血栓形成。45%的病人死亡率與支架血栓形成相關。過早停用抗血栓治療藥物,尤其是氯吡格雷通常會引起支架血栓形成。60%的病人由於使用了未經批准使用的支架同樣會增加了支架血栓形成的發生率。在裸金屬支架和藥物洗脫支架治療中,氯吡格雷和阿司匹林都是預防支架血栓形成的基礎性藥物。關於兩聯抗血栓治療的藥物最佳持續使用時間仍有爭議。食品藥物管理局和美國心臟協會/美國大學的心臟學家和各個相關學科的學者對兩聯抗血栓治療持續時間的建議為:使用藥物洗脫支架的患者最佳治療時間為一年,對使用裸金屬支架的患者為六個月。所有使用冠脈支架治療的患者必須終身服用阿司匹林藥物。隨著經皮腔內冠狀動脈血管成形術作為冠狀動脈硬化治療手段的引入,經皮冠狀動脈介入治療經歷了從單一的球囊擴張導管到複雜機械化的管腔內支架的戲劇化轉變。這一系列的進展影響著圍術期的用藥。本文作者在第一部分回顧了經皮冠狀動脈介入治療的進展並進行關於經皮腔內冠狀動脈血管成形術和冠脈支架術的討論;在第二部分作者將對冠狀動脈支架對非心臟病性外科手術術中問題和使用策略進行了討論。

(趙嫣紅 陳傑 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.

 

胸內血容指數可作為評估急性迴圈衰竭危重病人機體容量反應的一個指標:與中心靜脈壓的比較

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:胸內血容指數(ITBVI)和中心靜脈壓(CVP)常用於評估急性迴圈衰竭危重病人(收縮壓小於90 mmHg或者需要血管升壓藥的病人)的液體容量,然而它們之間未曾比較。

方法:在這項前瞻性干預研究中,作者選擇35名(其中男性21名)鎮靜下行機械輔助呼吸且監測心排血量(採用漂浮導管,溫度稀釋法)的急性迴圈衰竭病人。機體容量反應定義為休克指數(心輸出量/心率/體表面積)升高大於15%。記錄ITBVICVP變化特徵曲線。

結果51%患者在液體衝擊試驗後休克指數升高大於等於15%(為陽性反應)。基礎血流動力學資料在陽性者與陰性者之間無差異。ITBVI的特徵曲線下面積是0.64(95%CI0.46-0.80),而CVP0.6895CI0.46-0.80),兩者無統計學差異(P0.73)。CVPITBVI的最佳甄別閾分別是9mmHg.(靈敏度=61%,特異性=82%)和928 mmHg(靈敏度=78%,特異性=53%)。

結論ITBVI在評估急性迴圈衰竭危重病人的液體容量方面,與CVP有著相似的價值。

(葉樂 陳傑 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.

 

隨機藥物抽檢減少麻醉住院醫師藥物依賴發生率:來自一個研究方案的初步結果

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.

 

麻醉住院醫師的藥物濫用率約為1%-2%,幾乎80%的研究方案中有一個或多個住院醫師存在上述問題。教育和藥物控制未能減少藥物濫用的發生率。麻醉醫生職業責任為患者提供良好用藥.作者建立一個方案通過隨機抽驗麻醉科住院醫師尿液來嘗試減少藥物濫用發生率。儘管有邏輯上和文化上問題,作者認為這方案易於施行。更大的多機構的研究是必須的以確定是否需制定隨機尿檢以減少麻醉住院醫師的藥物濫用發生率。

(丁俊雲 陳傑 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-甲基巴豆醯輔酶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.

 

有先天性代謝障礙的病人在圍術期需特殊考慮。下文的病例報告中,作者成功處理了一例3-甲基巴豆醯輔酶A羧化酶缺乏症的病人,疾病導致繼發性肉毒堿缺乏和β 氧化功能障礙。患者可能存在潛在的心肌病,在應激狀態下有代謝失代償、酸中毒、低血糖的危險。

(杜唯佳 陳傑 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.

 

乳癌術後病人自控椎旁鎮痛的可行性:兩種方法的前瞻性、隨機雙盲研究的比較

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:椎旁鎮痛用於乳房術後是有效的。PCIA或者PCEA用於術後鎮痛的效果已經被很好的證明。本研究目的是將椎旁鎮痛應用到病人自控鎮痛中,並且評估兩種不同方法的效應和耐受性。

方法:參與此次隨機雙盲試驗的是乳癌術後患者,隨機分成兩組進行兩種不同方法的自控椎旁鎮痛:19名病人接受0.2%的左旋布比卡因,持續劑量8ml/hPCA劑量3ml,鎖定時間15分(15分鎖定組);18名病人接受0.2%的左旋布比卡因,持續劑量4ml/hPCA劑量8ml,鎖定時間30分(30分鎖定組)。主要預後指標一是動態疼痛評分(視覺疼痛評分量表),間隔4小時一次,進行36個小時。另一指標是靜息疼痛評分,包括援救鎮痛藥物的需要量,左旋布比卡因的用量,需要量,PCA劑量和患者的滿意度。

結果:靜息和動態的疼痛評分分組進行比較。15分鎖定組中有2名患者和30分鎖定組有5名患者要援救鎮痛藥物(P=0.23)。兩組病人接受的左旋布比卡因的量分別是15分鎖定組400±95ml30分鎖定組330±130mlP=0.012)。15分鎖定組病人需要單次注射次數是75±16次,30分鎖定組為69±14次(P=0.4)。然而,15分鎖定組病人接受的PCA次數是39±22次,30分鎖定組則只有24±16次(P=0.02)。收縮壓,心率,呼吸頻率,鎮靜評分,噁心,止吐藥物的需要量和滿意度兩組是相似的。

結論:乳癌術後病人自控椎旁鎮痛的兩種方法都可以提供滿意的鎮痛效果並具有和很好耐受性。

(舒慧剛 陳傑 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.

 

長時使用嗎啡損害小鼠血管形成和內皮原細胞的活動

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:嗎啡是一種治療傷口疼痛最普通的處方藥之一,本研究用一個帶有受傷創口的小鼠做模型,觀察大劑量嗎啡對血管發生和內皮原細胞活動的影響。

方法:在小鼠身上制一切開傷口,用安慰劑或嗎啡(20mg/kg, ip)治療14天。通過測試用藥前傷口的面積和用藥後傷口面積的比例來比較傷口的癒合,通過魯米若增強發光劑來檢測傷口區超氧化物陰離子的濃度, 分離迴圈的單核細胞並計內皮原細胞數目(確定為CD34+/CD133+細胞),用Matrigel(基質膠)測定法測定在體和離體經過嗎啡治療後血管形成情況。

結果:嗎啡組比對照組小鼠傷口癒合減慢,傷口周圍的超氧化物離子高。嗎啡減少傷口內皮原細胞的活動數目,基質膠測定法顯示嗎啡損害動物血管形成,用嗎啡處理過的培養的內皮細胞顯示動物血管發生受損及毛細血管形成減少。

結論:大劑量嗎啡損害血管發生,增強系統氧化應激增強及內皮原細胞活動受損。本研究強調系統給予大劑量嗎啡對血管發生存在潛在的有害作用。

(劉世文 陳傑 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.

 

影響局麻藥在硬膜外麻醉神經阻滯平面的因素及腰段和胸段硬膜外麻醉的比較

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.

 

在不同的個體中,一定劑量的局麻藥在硬膜外腔擴散的感覺阻滯是有個體差異的,影響因素仍有爭論。基於最近關於硬膜外神經阻滯的研究結果,特別是胸段的硬膜外麻醉,作者發現局麻藥的總容量似乎在決定感覺平面、交感神經、運動神經阻滯等發麵起主要作用,硬膜外針或導管的位置決定阻滯神經的類型。年齡可能與感覺阻滯平面有一定的相關性,胸部的硬膜外神經阻滯比腰部更為明顯。病人的特徵及技術細節,如病人的體位元、麻醉操作方式及注射速度,只能在感覺障礙分佈方面起到很小的作用,或者說這些影響是不確定的。然而,很多病人因素和技術因素的結合可以幫助預測局麻藥劑量的需求。基於這些研究結果,作者認為可以根據不同外科手術在鎮痛和交感阻滯要求而優化硬膜外穿刺點。

(張磊 陳傑 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.

預防性應用止吐藥物對嘔吐高危患者出院後噁心嘔吐發生率及恢復期生活功能性品質的影響:一項前瞻、隨機、雙盲比較兩種預防性止吐方案的試驗研究

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:比較兩種預防性應用止吐藥物的方法預防出院後噁心嘔吐的效果以及對患者恢復期生活品質的影響。

方法:64例行門診婦科手術且存在嘔吐高危風險的女性患者隨機分為兩組:試驗組術中靜脈注射地塞米松8 mg及恩丹司瓊4 mg,隨後在出院時及術後第1天、第二天早晨分次口服8 mg恩丹司瓊片劑。對照組術中只靜脈注射恩丹司瓊4 mg。在麻醉後恢復室及出院後通過電話隨訪5天每日1次評價惡性嘔吐症狀以及疼痛的發生率及嚴重程度。用一項修訂的嘔吐功能性生活指數來評估對恢復期生活品質的影響。

結果:共有60例患者完成了這項實驗,每組各30例。出院後,從麻醉後第8h到第120h期間噁心的發生率對照組和試驗組分別為57%20%,嘔吐的發生率兩組分別為20%3%(P < 0.05)33%的試驗組患者及60%的對照組患者均報告有嘔吐症狀,對其生活品質產生了不良影響(P < 0.05)

結論:與單次術中靜脈注射恩丹司瓊預防性應用相比,術中加地塞米松及術後每天一次恩丹司瓊能顯著降低出院後噁心嘔吐的發生率,並減少對術後恢復期前5天生活品質的不良影響。

(邱鬱薇 馬皓琳 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.


 

評價3種不同劑量的帕洛諾司瓊與安慰劑在術後72小時內防止術後噁心嘔吐的有效性和安全性的隨機雙盲研究

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:我們設計這個多中心、隨機、雙盲的研究來評估3種不同劑量的帕洛諾司瓊與安慰劑對於術後72小時內術後噁心嘔吐(PONV)的發生及嚴重程度影響的有效性和安全性。

方法:行擇期婦科或者乳腺手術的女性患者,根據另外2PONV風險因素(不吸煙狀況和PONV/或暈動病病史)分層。544名有以上有1個或2個風險因素的患者在麻醉誘導前即刻隨機靜脈注射一種劑量的帕洛諾司瓊(0.025 mg0.050 mg0.075 mg)或安慰劑。術後0-24小時和24-72小時兩時間段的主要有效性指標為完全有效(CR:沒有嘔吐並且沒有使用緩解藥物)。

結果:安慰劑和0.075 mg帕洛諾司瓊的術後0-24小時CR率為36%56% (P = 0.001)24-72小時CR率為52%70% (P = 0.002)0-72小時CR率為36%52% (P = 0.010)0.075 mg帕洛諾司瓊與安慰劑相比在0-24小時內(P < 0.001)噁心程度較小(接近“輕度”或“無”),而且顯著延遲了出現嘔吐時間(P = 0.002)和治療失敗時間(P = 0.004)的中位數。儘管在統計學上0.025 mg0.050 mg劑量的帕洛諾司瓊CR率在0-24小時和24-72小時時間段內並不優於安慰劑,但是較低的劑量可以在0-24小時內緩解噁心的嚴重程度(P = 0.040P = 0.004)

結論:單次靜脈注射0.075mg帕洛諾司瓊能有效地緩解入院手術患者術後噁心的嚴重程度,並且推遲嘔吐和治療失敗的時間;低劑量就不是那麼有效。

(唐亮   馬皓琳 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.


 

病人危險因素與其術後早期以及後期發生嘔吐症狀的相關性分析

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

背景術後噁心嘔吐(PONV)仍然是擇期手術術後常見的併發症,因此常常對具有發生PONV的已知危險因素的病人預防性應用止吐藥物。我們設計這次前瞻性觀察研究的目的就是來評價病人發生PONV的常見危險因素與其術後早期(0–24 h)以及晚期(24–72 h)發生嘔吐症狀的關聯性。

方法:130名擬行擇期腹腔鏡手術(n = 88)或整形手術(n = 42)的病人根據Apfel風險評分系統算出其發生PONV的風險分數。Apfel風險評分系統給女性、不吸煙者、有PONV或暈動病史以及術後阿片類藥物的使用四個危險因素各記一分。假定所有病人都將在術後接受阿片類鎮痛藥。所有病人預防性接受0123種止吐藥物。術後分別在06h624h以及2472h時段內評價噁心嘔吐的發生情況以及需要止吐藥物來補救治療的情況。另外,用標準化的病人問卷來評價PONV對正常日常生活活動恢復的影響。

結果:Apfel風險評分分別為234分的組中分別有87%90%95%病人預防性應用一種或更多種的止吐藥。當危險因素為3個或者4個時,分別有56% 75%的病人接受了≥2種止吐藥。在術後06h時段內,三個危險因素組和四個危險因素組分別有11% 22%的病人發生嘔吐,而兩個危險因素組有6%的病人發生嘔吐;在術後6–24 h時段內,嘔吐的發生率分別為13%27% (0%)。然而,在術後24–72 h時段內,三組嘔吐的發生率均低且組間沒有差別(分別為9% 5%11%)。術後0–6 h 以及6–24 h時段內高危險因素組中中到重度噁心的發生率增高(分別為19%–28%6% 20%–30%9%)。然而,術後24–72 h時段內三個危險因素組和四個危險因素組噁心的發生率與兩個危險因素組沒有差別(5%8%6%)。四個危險因素組對補救止吐藥的需要和嘔吐症狀對正常活動的干擾與兩個和三個危險因素組相比明顯提高。

結論:儘管常常預防性使用多種止吐藥物,Apfel風險評分為34(與2相比)仍與術後首個24小時內較高的嘔吐發生率相關。然而,後期(24–72 h)嘔吐症狀的發生率低且似乎與病人的Apfel風險評分沒有關係。

(吳進   馬皓琳 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.



全麻藥對三種配體門控的離子通道有相加作用

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:本研究旨在確定成對的化合物包括全麻藥,是否能夠以一種協同的方式同時調製受體功能,以此來證明蛋白記憶體在多處麻醉藥結合部位。

方法:通過使用標準的電生理方法,我們測定了包括苯、異氟烷(ISO)、氟烷(HAL)、氯仿、氟硝西泮、鋅以及戊巴比妥至少一種藥物以上複合對以下至少一種配體門控離子通道的作用:N-甲基-d-天冬氨酸受體、甘氨酸受體以及{gamma}-氨基丁酸A型受體。

結果:所有藥物-藥物-受體的結合都被發現呈相加而非協同性調製作用。ISO+苯呈累加性地抑制N-甲基-d-天冬氨酸受體功能。ISOHALISO+鋅一樣,呈累加性地增強甘氨酸受體功能。ISOHAL和以下組合(HAL+氯仿、戊巴比妥+ISO、氟硝西泮+ISO)一樣,呈累加性地增強{gamma}-氨基丁酸A型受體功能。

結論:同時發生的全麻藥對配體門控離子通道的變構調製作用完全是相加性的。而成對的全麻藥協同性地產生全身麻醉作用,必然基於較單個受體更為複雜的系統。

(黃施偉 譯,馬皓琳 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.



成人肌肉乙醯膽鹼受體的成對競爭性拮抗劑之間的協同作用

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:臨床上已經研究發現某些特定成對的煙鹼乙醯膽鹼受體(nAChR)競爭性拮抗劑的神經肌肉阻滯的協同作用。協同作用的機制還沒有闡明。我們驗證了這一假說,即協同作用源於拮抗劑在成人nAChR的兩個配體結合位點的不同的選擇性。

方法:我們在BOSC23細胞中表達了nAChR。在同時應用或無拮抗劑的情況下,我們在膜外面向外式膜片應用了乙醯膽鹼,並且在室溫下測量了可見電流。我們測定了(+)-筒箭毒堿、甲筒箭毒、呱庫溴銨、維庫溴銨、順式阿曲庫銨、羅庫溴銨和阿曲庫銨的IC90。對於兩種拮抗劑的15種組合,我們測定了在第二種拮抗劑的IC70存在的情況下某種拮抗劑的IC90。我們繪製了90%抑制時的等效線圖。對於單一的拮抗劑,我們測定了包括{epsilon} {delta}亞單元中的變異在內的受體抑制作用來確定位點選擇性。

結果:兩對拮抗劑,甲筒箭毒和順式阿曲庫銨以及順式阿曲庫銨和阿曲庫銨呈相加作用。10種組合,包括(+)-筒箭毒堿和呱庫溴銨以及呱庫溴銨和維庫溴銨,具有高度的協同性,以至於這種組合比期望的相加作用強2-3倍。3種組合比期望的相加作用強1.5-1.6倍。(+)-筒箭毒堿和甲筒箭毒的抑制作用僅對{epsilon}亞單元的突變敏感。維庫溴銨僅受{delta}亞單元的突變的影響。其他拮抗劑的抑制作用可以被任一亞單元的突變所減低。

結論:很多拮抗劑的組合呈現出了對成人nAChR的協同作用。在結構上相似和不相似的拮抗劑觀察到了協同作用。協同作用的程度並不總是與測定的突變位點特異性良好地相關。在某些,但不是全部的例子中,受體水準的協同作用與臨床測定的協同作用相關。我們得出結論,肌肉鬆弛劑的協同作用的部分原因是與成人nAChR的直接相互作用。

(黃麗娜 馬皓琳 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.



聽覺誘發電位的卡嗒聲對雙頻譜指數和熵的影響

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:聽覺誘發電位(AEP)的卡嗒聲對腦電圖指數和雙頻譜指數(BIS)會產生一定的影響,但是很多研究都測量了同時產生的指數卻沒有涉及這種影響。在本次研究中我監測了這種AEP的卡嗒聲對BIS以及對熵監護儀測得的反應熵(RE)和狀態熵(SE)的影響。

方法:四十位年齡在4070歲之間擇期在脊麻下行下肢手術的病人,用藥為0.5%的布比卡因或丁卡因。病人鎮靜用1mg咪達唑侖,隨後丙泊酚輸注,開始速度1 mg · kg–1 · h–1。控制輸注丙泊酚以使BISSE806040保持幾分鐘,然後給予65分貝的AEP卡嗒聲60秒。卡嗒聲停止後持續60 秒觀察BISRESE的變化。

結果:在卡嗒聲過程中BISRESE值顯著增加。當BISSE值為60時這種增強作用持續時間最長。

結論:在脊麻時丙泊酚輸注產生的不同程度的鎮靜過程中,AEP的卡嗒聲可以一過性增強同時測定的BISRESE。因此,當AEP和這些監測指標同時應用于一個病人時,前者的卡嗒聲對這些指標的影響必須要加以考慮。

(姜旭暉譯,馬皓琳 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.



死後的生命:圍術期災禍的後果

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

大多數麻醉醫師在其職業生涯中,會經歷圍術期患者死亡或較大的圍術期災禍。然而,麻醉訓練沒能使個人準備好處理此類應激事件的後果。多重調查顯示:病人的死亡會對高達75%的有關衛生保健提供者產生較大的情緒影響,無論死亡是否為意料中或患者是否和醫生熟識。心理上的復原通常需要數周或數月,並且,因缺乏情緒和專業支持而受阻礙。資料表明:大多數麻醉醫生會青睞更正式的支援結構,包括從臨床工作休息的選擇權。即使圍術期災禍後專業功能的正式評估還未進行,英國和愛爾蘭麻醉醫師協會指定了推薦多級支援的指南,而在麻醉病人安全基礎網站上的可用的“不利事件記錄”提供了一系列步驟,以使患者損傷降到最低並在發生不良麻醉事件後鑒定其原因。在此類事件發生後未能妥善處理的負面後果同樣對個人和衛生保健系統有重要意義。圍術期災禍對於提供者和衛生系統的短期和長期影響的更進一步研究是必要的。另外,如何處理圍術期災禍後果的教育和正式支援結構應當提供給各水準訓練中的行醫者。

(唐李雋    馬皓琳  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.



陰部神經阻滯用於會陰切開術後疼痛緩解的隨機對照研究

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:分娩過程中的會陰切開術或會陰撕裂引起產後期的顯著疼痛。我們設計了這項隨機雙盲對照試驗以研究神經刺激器引導下單側會陰神經阻滯對會陰切開術後疼痛的緩解效果。

方法:40位元陰道分娩過程中需要會陰正中旁切開的產婦隨機分為兩組:在會陰切開修補後用15mL7.5mg/mL羅呱卡因(試驗組)或生理鹽水(對照組)行會陰神經阻滯。用會陰切開術後36122448 h時靜息狀態及活動(步行和坐)過程中的VAS評分來評價會陰切開的疼痛。難以忍受的疼痛(VAS>30 mm)則用每12h 700mg尼氟酸栓劑予以治療。主要結果變數為會陰切開後48h內靜息及活動時的疼痛評分。

結果:兩組間人口統計學和產科特徵方面均無差異。所有病人都成功完成了會陰神經刺激。試驗組患者產後36122448 h時靜息狀態時的疼痛評分顯著低於對照組(P < 0.05),在坐和步行時同樣也獲得了更好的鎮痛效果。試驗組和對照組分別有3(15%)17位元(85%)病人需要額外鎮痛治療(P < 0.001)

結論:此項研究顯示用7.5mg/mL羅呱卡因行神經刺激器引導下的單側會陰神經阻滯可以減弱會陰切開術後初始48h內的疼痛,並減少額外鎮痛藥的需要量。

(黃佳佳譯,馬皓琳 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.



右美托咪定靜脈給藥減少大鼠顱內高壓引起的肺通透性

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:腦池內右美托咪定(DEX)減少顱內高壓大鼠的心功能不全。然而,在顱內高壓期間右美托咪定靜脈給藥對心功能和肺通透性方面的影響還未被評估過。我們假設右美托咪定靜脈給藥能減少大鼠顱內高壓引起的血流動力學改變和肺通透性,並進行測試。

方法:氟烷麻醉並機械通氣的大鼠分成4組。其中兩組置入硬膜下帶氣囊的導管,充氣60s以產生顱內高壓。顱內高壓前和後30min行動脈血氣分析。平均動脈壓、心率、顱內壓持續監測30minDex組(n=8)靜脈給右美托咪定首量80 µg/kg,繼而6 µg · kg–1 · min–1(40 µg/mL)持續10 min,對照組(n=8)靜脈給生理鹽水首量2 mL/kg,繼而0.15 mL · kg–1 · min–1持續 10 min。非顱內高壓下施行手術,分為給右美托咪定(偽裝-Dex組,n=5)和不給右美托咪定(偽裝-對照, n = 5)。所有組用伊文思藍染色滲出技術測量肺通透性。處死前2h給予伊文思藍染料20 mg/kg,並用雙波長分光光度分析技術量化血漿和肺組織中的伊文思藍。

結果:各組間基礎動脈壓、心率、Pao2 均無顯著性差異。對照組中,顱內高壓短暫地增加平均動脈壓和心率,隨即迅速下降進入平臺期。在Dex組,平均動脈壓短暫升高,然後迅速降至基線,然而顱內高壓時心率並未變化。顱內高壓後DexPao2比對照組高[138 (127–169)78 (59–124) mm Hg, 中位數 (範圍), P < 0.01]。肺通透性指數Dex組比對照組低[430 (182–450)570 (427–1170), P < 0.01]。但偽裝-Dex組比偽裝-對照組高[25 (24–35)6 (4–7), P < 0.01]

結論:預防性靜脈給予右美托咪定能減少大鼠顱內高壓引起的肺通透性和血流動力學變化。

(朱 慧譯 馬皓琳 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.



在特別1點上的針壓法對插針主觀和自主反應的影響

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:術前鎮靜藥可以減少創傷性麻醉操作的不適感。一些研究者表示在針刺特別1點上的針壓法有鎮靜效果。我們研究在特別1點上的針壓法是否能減輕插針的疼痛。

方法:我們用口述等級量表(VRS)疼痛分數和心率變異性(HRV)研究針壓特別1點和假點對插針的效果。22例健康女性志願者隨機分為2組:特別1點組接受針壓法針壓特別1點,假點組接受針壓假點。心電圖記錄開始後,27號針插入前臂皮膚。隨後,在針壓法過程中另一個針頭插入另一前臂皮膚。

結果:針壓特別1點明顯減輕VRS,但針壓在假點能增加VRS。針壓特別1點明顯減輕HRV對針刺的低頻率/高頻率反應。

結論:與假點比較,針壓特別1點明顯減輕插針疼痛。針壓特別1點明顯減少插針引起HRV低頻率/高頻率反應,表明減少交感神經系統活性。
(彭中美 馬皓琳 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.



調控鈣內流可以調節大鼠背根神經節細胞膜興奮性

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:神經元損傷導致的慢性神經性疼痛至今仍治療困難,部分的原因是疼痛的細胞機制還不完全清楚。我們以往的研究顯示,在齧齒類動物慢性神經性疼痛模型中,通過感覺神經元質膜的鈣離子內流明顯降低,但鈣電流喪失對感覺神經功能的直接後果並未確定。因此我們研究了與鈣內流消失相關的,神經損傷後神經膜性質變化,尤其是其興奮性提高到哪種程度會導致慢性疼痛。

方法:從未受損傷的大鼠背根神經節上分離A型神經元,用細胞內微電極進行測定。在測定興奮性和生物物理學常數時,改變記錄條件以抑制或增強鈣內流。

結果:降低外部浴槽中鈣離子的濃度或用浴槽鎘阻斷鈣內流,都使後超極化的持續時間和面積減少,並伴有動作電位初始的電流閾值的降低和持續去極化期間的反復觸發增多。相反地,提高細胞外液鈣離子濃度可以增強細胞後超極化,抑制反復觸發。神經元超極化時膜電位下降,是由陽離子非選擇性H電流造成的,降低浴槽中鈣離子的濃度、用鎘阻斷鈣電流,或細胞內鈣離子的螯合劑都會抑制這個電流。使用鈣內流亞型的選擇性阻滯劑的研究提示,N-P/QL- R-型電流對細胞後超極化的產生均有影響,且阻斷任何一種鈣通道電流,均會降低動作電位的上升速度,延長動作電位時程,且(除了L型鈣通道)降低引發動作電位的電流閾值。

結論:總之,我們的研究顯示抑制內向鈣電流會降低後超極化,減少超極化誘發的電壓降低,提高感覺細胞元的興奮性,重複這樣的改變可能導致外周神經的損傷。這說明,損傷的感覺神經元中內向鈣電流的降低會引發其功能障礙和過度興奮,並可能導致神經性疼痛。

(張瑩譯  馬皓琳 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.



不同濃度及容量的局麻藥行連續膕窩坐骨神經阻滯的效果:一項雙中心、隨機、對照研究

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:對於影響持續周圍神經阻滯作用的主要因素是局麻藥濃度還是僅為總藥量,尚未明瞭。因此我們檢驗了這樣一個檢驗假設,即使用不同濃度及速率、但總劑量相等的羅呱卡因行連續膕窩坐骨神經阻滯產生的效果相似。

方法:選擇行中度疼痛的腳踝或腳踝遠端部位矯形手術的患者,術前均從後膕窩徑路插入神經周圍導管到坐骨神經附近。術後將患者隨機分成兩組:術後第二天神經周圍輸注羅呱卡因0.2% (基礎 8 mL/h,單次加量 4 mL) 0.4% (基礎4 mL/h, 單次加量2 mL)。因此,兩組患者在每個小時內都接受了16 mg的羅呱卡因,通過病人自控的單次加量,每30分鐘可能接受額外的8 mg。主要觀察指標為從術後早晨開始的24小時內令人不快的肢體失去知覺的發生率。次要觀察指標包括鎮痛及病人滿意度。

結果:與0.4%羅呱卡因組患者(n = 25)經歷肢體無知覺0.6 (1.1) 〔均數(標準差)〕次比較,0.2%羅呱卡因組(n = 25)1.8 (1.8)次,(估計的差異=1.295%可信區間,0.3–2.0次;P = 0.009)。相反,鎮痛及滿意度各組相似。

結論:對於連續膕窩坐骨神經阻滯,局麻藥的濃度及容量影響其阻滯特性。使用較大容量相對低濃度的羅呱卡因時,患者肢體失去知覺更常見。因此在行連續膕窩坐骨神經阻滯時,使用相對高濃度較低容量的羅呱卡因似乎更可取。

(裘毅敏譯,馬皓琳、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.