Table of Contents

June 2008

 

CARDIOVASCULAR ANESTHESIOLOGY:

經皮吹入氧氣並不能改善心臟手術病人胸骨傷口的氧合

章一靜譯,薛張綱校

Transdermal Oxygen Does Not Improve Sternal Wound Oxygenation in Patients Recovering from Cardiac Surgery

Mohamed H. Bakri, Hassan Nagem, Daniel I. Sessler, Ramatia Mahboobi, Jarrod Dalton, Ozan Akça, Eric E. Roselli, and Steven R. Insler

Anesth Analg 2008 106: 1619-1626.

低體溫和酸中毒對人全血的凝血有協同損害作用

唐李雋    馬皓琳  李士通

Hypothermia and Acidosis Synergistically Impair Coagulation in Human Whole Blood

Daniel Dirkmann, Alexander A. Hanke, Klaus Görlinger, and Jürgen Peters

Anesth Analg 2008 106: 1627-1632.

PEDIATRIC ANESTHESIOLOGY:

評估麻醉藥物作用的策略和實驗模型:對神經系統發育的影響

陶穎瑩 陳傑

Strategies and Experimental Models for Evaluating Anesthetics: Effects on the Developing Nervous System (Special Article)

Cheng Wang and William Slikker, Jr

Anesth Analg 2008 106: 1643-1658.

對新生兒大腦的神經保護對策

宣麗真譯 薛張綱校

Neuroprotective Strategies for the Neonatal Brain (Review Article)

Vincent Degos, Gauthier Loron, Jean Mantz, and Pierre Gressens

Anesth Analg 2008 106: 1670-1680.

全身麻醉藥對腦結構發育和神經認知功能的影響

張瑩譯  馬皓琳 李士通校

An Assessment of the Effects of General Anesthetics on Developing Brain Structure and Neurocognitive Function (Review Article)

Andreas W. Loepke and Sulpicio G. Soriano

Anesth Analg 2008 106: 1681-1707.

全身麻醉誘導新生小鼠脊髓凋亡性神經退行性變

於章傑 陳傑

General Anesthetics Induce Apoptotic Neurodegeneration in the Neonatal Rat Spinal Cord (Review Article)

Robert D. Sanders, Jing Xu, Yi Shu, Antonio Fidalgo, Daqing Ma, and Mervyn Maze

Anesth Analg 2008 106: 1708-1711.

小計量異丙酚引起乳鼠大腦神經元凋亡

夏俊明譯 薛張綱校

Subanesthetic Doses of Propofol Induce Neuroapoptosis in the Infant Mouse Brain (Brief Report)

Davide Cattano, Chainllie Young, Megan M.W. Straiko, and John W. Olney

Anesth Analg 2008 106: 1712-1714.

右美托咪啶經鼻給藥與口服咪達唑侖在小兒麻醉術前用藥中的比較:一項雙盲隨機對照試驗

慧譯 馬皓琳 李士通校

A Comparison of Intranasal Dexmedetomidine and Oral Midazolam for Premedication in Pediatric Anesthesia: A Double-Blinded Randomized Controlled Trial (Brief Report)

Vivian M. Yuen, Theresa W. Hui, Michael G. Irwin, and Man K. Yuen
Anesth Analg 2008 106: 1715-1721

AMBULATORY ANESTHESIOLOGY:

喉顯微外科手術期間七氟烷吸入麻醉和丙泊酚/瑞芬太尼靜脈麻醉對唾液分泌的影響:一項前瞻性、隨機、對照研究

杜唯佳 陳傑

Jin Gu Kang, Jin Kyoung Kim, Han-Sin Jeong, Soo-Chan Jung, Moon Hee Ko, Shin Hong Park, Jae Keun Cho, Gil Joon Lee, Ji Won Choi, and Byung Dal Lee

A Prospective, Randomized Comparison of the Effects of Inhaled Sevoflurane Anesthesia and Propofol/Remifentanil Intravenous Anesthesia on Salivary Excretion During Laryngeal Microsurgery

Anesth Analg 2008 106: 1723-1727.

術前口服Passiflora減輕門診病人的焦慮:一項雙盲,安慰劑控制的研究

孫鵬飛譯 薛張綱校

Preoperative Oral Passiflora Incarnata Reduces Anxiety in Ambulatory Surgery Patients: A Double-Blind, Placebo-Controlled Study

Ali Movafegh, Reza Alizadeh, Fatimah Hajimohamadi, Fatimah Esfehani, and Mohmad Nejatfar

Anesth Analg 2008 106: 1728-1732.

補充供氧能否減少術後噁心嘔吐?隨機對照實驗的薈萃分析

吳進   馬皓琳 李士通

Does Supplemental Oxygen Reduce Postoperative Nausea and Vomiting? A Meta-Analysis of Randomized Controlled Trials

Mukadder Orhan-Sungur, Peter Kranke, Daniel Sessler, and Christian C. Apfel

Anesth Analg 2008 106: 1733-1738.

ANESTHETIC PHARMACOLOGY:

腹腔鏡下減肥手術期間輸注右旋美托咪啶:對復蘇的影響

張燕 陳傑

Dexmedetomidine Infusion During Laparoscopic Bariatric Surgery: The Effect on Recovery Outcome Variables

Burcu Tufanogullari, Paul F. White, Mariana P. Peixoto, Daniel Kianpour, Thomas Lacour, James Griffin, Gary Skrivanek, Amy Macaluso, Mary Shah, and David A. Provost

Anesth Analg 2008 106: 1741-1748.

在人低劑量吸入七氟醚後可以減少粒細胞-血小板的聚集作用

施穎譯,薛張綱校

Delayed Inhibition of Agonist-Induced Granulocyte-Platelet Aggregation After Low-Dose Sevoflurane Inhalation in Humans

Johannes Wacker, Eliana Lucchinetti, Marina Jamnicki, José Aguirre, Luc Härter, Marius Keel, and Michael Zaugg

Anesth Analg 2008 106: 1749-1758.

芳香族麻醉藥對傷害性刺激引起的背角神經元反應的作用

周雅春 李士通 馬皓琳

The Effects of Aromatic Anesthetics on Dorsal Horn Neuronal Responses to Noxious Stimulation

Aubrey Yao, JongBun Kim, Richard Atherley, Steven L. Jinks, Earl Carstens, Sean Shargh, Alana Sulger, and Joseph F. Antognini

Anesth Analg 2008 106: 1759-1764.

Rho激酶抑制劑可增強丙泊酚對大鼠支氣管平滑肌收縮的抑制作用

潘錢玲 陳傑

Rho-Kinase Inhibitors Augment the Inhibitory Effect of Propofol on Rat Bronchial Smooth Muscle Contraction

Motohiko Hanazaki, Masataka Yokoyama, Kiyoshi Morita, Atsushi Kohjitani, Hiroyasu Sakai, Yoshihiko Chiba, and Miwa Misawa

Anesth Analg 2008 106: 1765-1771.

延長使用異氟醚、丙泊酚、右旋美托咪定、氯胺酮對於成年鼠神經細胞增殖的影響

秦敏菊譯 薛張綱校

The Effect of Prolonged Anesthesia with Isoflurane, Propofol, Dexmedetomidine, or Ketamine on Neural Cell Proliferation in the Adult Rat

Avery Tung, Stacy Herrera, Casimir A. Fornal, and Barry L. Jacobs

Anesth Analg 2008 106: 1772-1777.

局麻藥氨苯丁酯抑制PC12細胞中總的和L-型鋇電流

黃施偉 譯,馬皓琳 李士通

The Local Anesthetic Butamben Inhibits Total and L-Type Barium Currents in PC12 Cells

Laurentius J.A. Rampaart, Jeroen P. Beekwilder, Gertrudis Th.H. van Kempen, Rutgeris J. van den Berg, and Dirk L. Ypey

Anesth Analg 2008 106: 1778-1783.

CTITICAL CARE AND TRAUMA:

評判手術病人外周血細胞比容的應用:不能很好反映真實血細胞容量

劉婷潔譯,薛張剛校

Peripheral Blood Hematocrit in Critically Ill Surgical Patients: An Imprecise Surrogate of True Red Blood Cell Volume

Danny M. Takanishi, Mihae Yu, Fedor Lurie, Elisabeth Biuk-Aghai, Hideko Yamauchi, Hao Chih Ho, and Alyssa D. Chapital

Anesth Analg 2008 106: 1808-1812.

CRITICAL CARE AND TRAUMA:

游離皮質醇在敗血症及感染性休克中的應用

裘毅敏   馬皓琳 李士通 校)

Free Cortisol in Sepsis and Septic Shock

Stepani Bendel, Sari Karlsson, Ville Pettilä, Pekka Loisa, Marjut Varpula, Esko Ruokonen For the Finnsepsis Study Group

Anesth Analg 2008 106: 1813-1819.

對血管內皮生長因數在嚴重膿毒症及膿毒性休克中的研究

劉沁譯 薛張綱校

Vascular Endothelial Growth Factor in Severe Sepsis and Septic Shock

Sari Karlsson, Ville Pettilä, Jyrki Tenhunen, Vesa Lund, Seppo Hovilehto, Esko Ruokonen For the Finnsepsis Study Group

Anesth Analg 2008 106: 1820-1826.

OBSTETRIC ANESTHESIOLOGY:

在七氟醚-氧化亞氮的全身麻醉下剖腹產手術中時BIS值的研究:初產婦和經產婦的比較。

王騰 陳傑

Bispectral Index Values During Sevoflurane-Nitrous Oxide General Anesthesia in Women Undergoing Cesarean Delivery: A Comparison Between Women With and Without Prior Labor

Kyung Y. Yoo, Cheol W. Jeong, Myung W. Kang, Seok J. Kim, Sung T. Chung, Min H. Shin, and JongUn Lee

Anesth Analg 2008 106: 1827-1832.

ANALGESIA:

腹部大手術術後給予氯胺酮可降低嗎啡用量:一項前瞻性、隨機、雙盲、對照研究

陳偉 陳傑

Postoperative Ketamine Administration Decreases Morphine Consumption in Major Abdominal Surgery: A Prospective, Randomized, Double-Blind, Controlled Study

Jérome Zakine, David Samarcq, Emmanuel Lorne, Mona Moubarak, Philippe Montravers, Sadek Beloucif, and Hervé Dupont

Anesth Analg 2008 106: 1856-1861.

複雜區域疼痛綜合征I型中血漿5羥色胺濃度升高

彭中美 馬皓琳 李士通

Increased Plasma Serotonin in Complex Regional Pain Syndrome Type 1

Feikje Wesseldijk, Durk Fekkes, Frank J. Huygen, Elly Bogaerts-Taal, and Freek J. Zijlstra

Anesth Analg 2008 106: 1862-1867.

圍術期使用加巴噴丁對整形外科病人鞘內注射嗎啡引起的術後瘙癢症的保護作用

王鵬 陳傑

Preoperative Gabapentin Prevents Intrathecal Morphine-Induced Pruritus After Orthopedic Surgery

Michael J. Sheen, Shung-Tai Ho, Chian-Her Lee, Yu-Chi Tsung, and Fang-Lin Chang

Anesth Analg 2008 106: 1868-1872.

大鼠內嗎啡肽的脊柱鎮痛效應:行為和G蛋白功能研究

張曦 譯,馬皓琳 李士通

The Spinal Antinociceptive Effects of Endomorphins in Rats: Behavioral and G Protein Functional Studies

Hong Xie, James H. Woods, John R. Traynor, and Mei-Chuan Ko

Anesth Analg 2008 106: 1873-1881.

大鼠脊髓腰段腺苷A2A受體的表達及對NMDA受體離子流的調節作用

趙燕星 陳傑

Expression of Adenosine A2A Receptors in the Rat Lumbar Spinal Cord and Implications in the Modulation of N-Methyl-d-Aspartate Receptor Currents

Emmanuel Guntz, Hélène Dumont, Els Pastijn, Alban de Kerchove d’Exaerde, Karima Azdad, Maurice Sosnowski, Serge N. Schiffmann, and David Gall

Anesth Analg 2008 106: 1882-1889.

鎮痛藥物曲馬多可以起到辣椒素暫態電位受體—1激動劑的作用

姜旭暉 馬皓琳 李士通

The Analgesic Drug, Tramadol, Acts as an Agonist of the Transient Receptor Potential Vanilloid-1

Rita Marincsák, Balázs I. Tóth, Gabriella Czifra, Tamás Szabó, László Kovács, and Tamás Bíró

Anesth Analg 2008 106: 1890-1896.

抗驚厥藥物的抗傷害性作用小鼠內臟疼痛模型

蔣宗明譯 薛張綱校

The Antinociceptive Effects of Anticonvulsants in a Mouse Visceral Pain Model

Radica M. Stepanovic-Petrovic, Maja A. Tomic, Sonja M. Vuckovic, Sonja Paranos, Nenad D. Ugresic, Milica S. Prostran, Slobodan Milovanovic, and Bogdan Boskovic

Anesth Analg 2008 106: 1897-1903.

伏核內多巴胺D2樣受體與氧化亞氮(N2O)的鎮痛作用

張江玲 陳傑

Dopamine D2-Like Receptor in the Nucleus Accumbens Is Involved in the Antinociceptive Effect of Nitrous Oxide

Sahoko Koyanagi, Shugaku Himukashi, Kumiko Mukaida, Tsutomu Shichino, and Kazuhiko Fukuda

Anesth Analg 2008 106: 1904-1909.

電神經刺激或超聲引導側位矢狀面的鎖骨下阻滯:隨機、對照、觀察者單盲的比較性研究

唐亮   馬皓琳 李士通

Electrical Nerve Stimulation or Ultrasound Guidance for Lateral Sagittal Infraclavicular Blocks: A Randomized, Controlled, Observer-Blinded, Comparative Study

Axel R. Sauter, Michael S. Dodgson, Audun Stubhaug, Anne Marie Halstensen, and Øivind Klaastad

Anesth Analg 2008 106: 1910-1915.

一項關於可樂定和膕窩神經組織阻滯後鎮痛持續時間的隨機、雙盲、安慰劑對照研究

黃凝譯  薛張綱校

Clonidine and Analgesic Duration After Popliteal Fossa Nerve Blockade: Randomized, Double-Blind, Placebo-Controlled Study

Jacques T. YaDeau, Vincent R. LaSala, Leonardo Paroli, Richard L. Kahn, Kethy M. Jules-Elysée, David S. Levine, Barbara L. Wukovits, and Jane Y. Lipnitsky

Anesth Analg 2008 106: 1916-1920.

 

評估麻醉藥物作用的策略和實驗模型:對神經系統發育的影響

Strategies and Experimental Models for Evaluating Anesthetics: Effects on the Developing Nervous System

Cheng Wang, MD, PhD, and William Slikker, Jr, PhD

From the National Center for Toxicological Research, U.S. Food & Drug Administration, Jefferson, AR.

Anesth Analg 2008 106: 1643-1658.

 

兒科及產科手術的發展使人們對麻醉持續時間及複雜性要求提高。有報導稱麻醉藥物能對發育中鼠大腦產生廣泛、劑量相關性的細胞凋亡。由於其他靈長類動物有著與人類相似的生理、藥理、代謝及繁殖系統,妊娠階段尤為顯著,所以猴一向被視為非常優良的評估麻醉藥物潛在神經毒性的動物模型。大腦對兒科麻醉藥物的神經作用的易感期受快速突觸發生過程(又稱大腦生長過程)的影響。為了將麻醉藥物對兒童可能的危害作用降至最低,麻醉操作中需考慮以下問題:

1.兒科麻醉中常用麻醉藥物(吸入麻醉藥、咪唑安定、氯胺酮及笑氣)與大腦細胞損傷間存在怎樣的相關性

2.是否要考慮類效應還是分別分析每種藥物的影響作用

3.是否存在麻醉藥物相互影響從而產生大腦細胞損傷

4.人類發育的哪一階段更易受麻醉藥物影響。

遺傳藥理/系統生物學方法對加深大腦相關性生物過程(包括神經元可塑性、神經毒性作用)的理解極為有用。由於神經毒性作用的表達存在複雜性及暫時性因素,所以遺傳藥理/系統生物學方法可以加強我們對麻醉藥誘導的生物過程的理解。而本綜述的主要目的是闡述使用這些方法、模型及相關保護措施尤其考慮到麻醉藥物誘導發育中神經細胞死亡這一問題。

本文之後許多討論基於的實驗都採用氯胺酮為主。這主要是由於早期的實驗以氯胺酮為主,且大量臨床前試驗如對於齧齒類動物及靈長類動物的麻醉藥物實驗也採用氯胺酮。儘管在兒科麻醉操作中氯胺酮使用相對有限,但相關研究的發現有力的證實其作用與n-甲基-d-天門冬氨酸拮抗劑相似。本文中作者對氯胺酮的著重講述並不意味氯胺酮比其他麻醉藥引起的神經退行性變可能性大,這只是由於我們已掌握的大量氯胺酮效應的基礎資料。

(陶穎瑩 陳傑 校)

Advances in pediatric and obstetric surgery have resulted in an increase in the duration and complexity of procedures requiring anesthesia. It has been reported that anesthetic drugs cause widespread and dose-dependent apoptosis in the developing rat brain. The similarity of the physiology, pharmacology, metabolism, and reproductive systems of the nonhuman primate to that of the human, especially during pregnancy, make the monkey an exceptionally good animal model for assessing potential neurotoxic effects of anesthetics. The window of vulnerability to these neuronal effects of pediatric anesthetics is restricted to the period of rapid synaptogenesis, also known as the brain growth spurt period. To minimize the risks to children resulting from the use of anesthesia, the following questions should be addressed:

1.              What is the relationship between exposure and brain cell loss for drugs commonly used in the practice of pediatric anesthesia (inhaled anesthetics, midazolam, ketamine, and nitrous oxide)?

2.              Are there "class effects," or does each drug need to be considered independently?

3.              Are there important interactions among the drugs used as anesthetics contributing to the risk of brain cell death?

4.              What is the likely period of human vulnerability?

Pharmacogeneomic/system biology approaches have great potential for helping to advance the understanding of brain-related biological processes, including neuronal plasticity and neurotoxicity. Because of the complexity and temporal features of how developmental neurotoxicity is manifested, pharmacogenomic/systems biology approaches may prove to be useful tools for enhancing our understanding of the biological processes induced by anesthetics. Therefore, the main purpose of this review is to describe the application of these approaches and models, as well as protection strategies, especially as regards the issue of anesthetic-induced neuronal cell death during development.

Much of the discussion that follows is based on experiments conducted with ketamine. This is due in part to the use of ketamine in the early studies and the volume of preclinical experimental work performed with this drug, as well as its use in anesthetic studies in developing rodents and nonhuman primates. Although ketamine use in pediatric anesthesia is relatively limited, the findings of the studies are sufficiently strong to merit concern about the N-methyl-d-aspartate antagonist drugs as a class. Our focus on ketamine should not be construed as implying that the risk of neurodegeneration with ketamine is greater, or less, than with other anesthetics. We are simply describing the effects where we have the most preclinical data.

 

全身麻醉誘導新生小鼠脊髓凋亡性神經退行性變

General Anesthetics Induce Apoptotic Neurodegeneration in the Neonatal Rat Spinal Cord

Robert D. Sanders, BSc, MBBS*, Jing Xu, MD{dagger}, Yi Shu, BSc*, Antonio Fidalgo, MSc*, Daqing Ma, MD, PhD*, and Mervyn Maze, MB ChB, FRCA, FRCP, FMedSci*

From the *Departments of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, Chelsea & Westerminster Hospital, London; and {dagger}Department of Anesthesiology, Gongli Hospital, Pudong, Shanghai, China.

Anesth Analg 2008 106: 1708-1711.

 

背景:麻醉藥物可觸發新生鼠大腦的凋亡性神經退行性變;然而這種神經退行性變是否會發生於脊髓--這一麻醉鎮痛藥物的重要靶點,仍然未知。

方法:7日齡鼠隨機暴露於空氣或75%笑氣-0.75%異氟醚-氧氣的混合氣體6小時(每組n19)。在氣體暴露結束時檢測腰部脊髓的細胞凋亡Caspase-3的含量(每組n3)。使用甩尾痛覺測試儀在出生後第8、第15、第三30天評價傷害反應的發育情況(每組n3)。在出生後第30d使用旋轉實驗評價運動反應。

結果:笑氣-異氟醚增加脊髓中的含細胞凋亡蛋白酶caspase-3神經元的數量(P < 0.01)。儘管損傷較多發生於脊髓腹側角,運動損傷並未發生(P > 0.05)。在測試的三個發育階段並沒觀察到小鼠對傷害的功能效應(P > 0.05)。

結論:麻醉藥物誘導新生鼠脊髓神經的凋亡;然而,這種損傷是否引起功能異常是未明的。麻醉藥物的使用並不影響運動或對傷害刺激的反應。需要進一步研究局麻技術是否有引起脊髓神經凋亡的潛在危害。

(於章傑 陳傑 校)

BACKGROUND: Exposure to anesthetics triggers apoptotic neurodegeneration in the neonatal rat brain; whether neuronal apoptosis also occurs in the spinal cord, a crucial target for analgesic and anesthetic drugs, is unknown.

METHODS: We exposed 7-day-old rats were exposed to air or 75% nitrous oxide + 0.75% isoflurane in oxygen for 6 h (n = 19 per group). Caspase-3 immunoreactivity was evaluated in the lumbar spinal cord at the end of the gas exposure (n = 3 per group). Developmental nociceptive responses were tested using tail flick latencies on postnatal days 8, 15, and 30 (n = 3 per group). Motor responses were evaluated using the rotarod on postnatal day 30 (n = 7 per group).

RESULTS: Isoflurane plus nitrous oxide increased the numbers of caspase-3 positive neurons in the spinal cord (P < 0.01). Despite a preponderance of the injury in the ventral horn of the spinal cord, motor impairment did not occur (P > 0.05). No functional effect on nociception was observed at the three developmental stages tested (P > 0.05).

CONCLUSIONS: Anesthesia induces apoptosis in the neonatal rat spinal cord; however, the functional consequences of this injury, if any, remain obscure. Neither motor nor nociceptive responses were affected by anesthetic treatment. Nonetheless, further investigation is required as regional anesthetic techniques may also trigger neuroapoptosis in the spinal cord with unknown potency.

 

喉顯微外科手術期間七氟烷吸入麻醉和丙泊酚/瑞芬太尼靜脈麻醉對唾液分泌的影響:一項前瞻性、隨機、對照研究

A Prospective, Randomized Comparison of the Effects of Inhaled Sevoflurane Anesthesia and Propofol/Remifentanil Intravenous Anesthesia on Salivary Excretion During Laryngeal Microsurgery

Jin Gu Kang, MD*, Jin Kyoung Kim, MD, PhD*, Han-Sin Jeong, MD, PhD{dagger}, Soo-Chan Jung, MD{dagger}, Moon Hee Ko, MD{dagger}, Shin Hong Park, MD{dagger}, Jae Keun Cho, MD{dagger}, Gil Joon Lee, MD{dagger}, Ji Won Choi, MD*, and Byung Dal Lee, MD, PhD*

From the Departments of *Anesthesiology and Pain Medicine, {dagger}Otorhinolaryngology—-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Anesth Analg 2008 106: 1723-1727.

 

背景:提供清晰的手術視野是喉顯微外科手術麻醉要求之一,因此期望麻醉藥產生較少的唾液分泌。七氟烷吸入麻醉和丙泊酚/瑞芬太尼全憑靜脈麻醉在喉顯微外科手術中被廣泛應用,然而,有關七氟醚和丙泊酚/瑞芬太尼各自對於唾液分泌影響的比較研究很少。

方法40名行喉顯微外科手術的患者隨機實施七氟醚或丙泊酚/瑞芬太尼麻醉。比較兩實驗組的唾液流速,唾液成分,手術操作前為了看清喉部解剖分層而進行的吸引次數,以及術後殘餘分泌物總量。

結果:丙泊酚/瑞芬太尼組實驗者的平均唾液分泌速度較七氟烷組明顯增高(0.53 ± 0.39 vs 0.28 ± 0.15 mL/min, P < 0.001)。手術操作前為了喉部分清晰而進行的吸引次數,在丙泊酚/瑞芬太尼組中也是明顯增多(5.0 ± 2.3 vs 2.1 ± 1.5, P < 0.001)。丙泊酚/瑞芬太尼組實驗者術後口腔和口咽部的平均殘餘分泌物總量也增多(2.13 ± 0.59 vs 0.45 ± 0.32 mL, P < 0.001)。此外,兩組收集的分泌物中還觀察到了氯離子濃度水準有明顯的差異(七氟烷組; 93 ± 19 vs 丙泊酚/瑞芬太尼組; 135 ± 58 U/L, P = 0.004)

結論:在喉部手術期間,丙泊酚/瑞芬太尼靜脈麻醉比七氟醚吸入麻醉的唾液分泌更加活躍。

(杜唯佳 陳傑 校)

BACKGROUND: One of the goals of anesthesia for laryngeal microsurgery is to provide a clear surgical view, and therefore anesthetics that produce less saliva are desirable. Sevoflurane inhalation anesthesia and total IV anesthesia with propofol/remifentanil are widely used for anesthesia during laryngeal microsurgery; however, few rigorous comparisons of the effects of sevoflurane and propofol/remifentanil on salivation have been performed.

METHODS: Forty subjects undergoing laryngeal microsurgery were randomly assigned for sevoflurane or propofol/remifentanil anesthesia. We prospectively compared the salivary flow rates, compositions, the number of suction episodes required to clearly view the laryngeal lesions before the main procedures, and residual secretion volume after the procedure in both groups.

RESULTS: The mean salivary excretion rate was significantly higher in the propofol/remifentanil group than in the sevoflurane group (0.53 ± 0.39 vs 0.28 ± 0.15 mL/min, P < 0.001). Before starting the main procedure, the number of suction episodes required to clearly view the laryngeal lesions was also higher in the propofol/remifentanil group (5.0 ± 2.3 vs 2.1 ± 1.5, P < 0.001). Mean residual secretion in the oral cavity and oropharynx after the procedure was greater in the propofol/remifentanil group (2.13 ± 0.59 vs 0.45 ± 0.32 mL, P < 0.001). In addition, a significant difference in chloride levels in collected secretion was noted (sevoflurane; 93 ± 19 vs propofol/remifentanil; 135 ± 58 U/L, P = 0.004).

CONCLUSIONS: Salivary excretion under propofol/remifentanil anesthesia is greater than under sevoflurane anesthesia during laryngeal surgery.

 

腹腔鏡下減肥手術期間輸注右旋美托咪啶:對復蘇的影響

Dexmedetomidine Infusion During Laparoscopic Bariatric Surgery: The Effect on Recovery Outcome Variables

Burcu Tufanogullari, MD*, Paul F. White, PhD, MD*, Mariana P. Peixoto, MD*, Daniel Kianpour, MS*, Thomas Lacour, MD*, James Griffin, MD*, Gary Skrivanek, MD*, Amy Macaluso, MD*, Mary Shah, MD*, and David A. Provost, MD{dagger}

From the Departments of *Surgery, {dagger}Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas.

Anesth Analg 2008 106: 1741-1748.

景:右旋美托咪啶,一種受體激動劑,有顯著的麻醉和鎮痛效應。作者設計這項前瞻性,隨機,雙盲,安慰劑對照研究,以評估在腹腔鏡下減肥手術後,右旋美托咪啶對術後早期和晚期復蘇品質的影響。

法: 80ASA II–III級病態肥胖性患者,隨機分為四組: 對照組輸注生理鹽水;右旋美托咪啶0.2組接受右旋美托咪啶0.2 µg · kg–1 · h–1;右旋美托咪啶0.4組接受右旋美托咪啶0.4 µg · kg–1 · h–1;右旋美托咪啶0.8組接受右旋美托咪啶0.8 µg · kg–1 · h–1。平均動脈壓維持在誘導前基礎值的±25 %。記錄圍手術期血流動力學,術後疼痛評分,復蘇期間應用鎮痛藥和止吐藥量等。評估術後1d2d7d疼痛程度,鎮痛藥的需求量,病人對疼痛處理的滿意度,康復品質,及飲食攝入的恢復和腸功能的恢復。

果:右旋美托咪啶0.20.40.8組地氟醚吸入濃度分別減少了19%,20%,和22%。但未能加快麻醉顯效。雖然四組中術中血流動力學相似,但麻醉後恢復室(PACU)右旋美托咪啶0.2 0.40.8組較對照組動脈血壓較低 P<0.05)。在右美托咪啶組PACU的停留時間明顯縮短(右美托咪啶組81 ± 31 87 ± 24min 對照組為104 ± 33 min, P < 0.05)。在PACU中芬太尼用量,右旋美托咪啶 0.20.40.8組比對照組顯著減少(分別為113 ± 85, 108 ± 67, and 120 ± 78 vs 187 ± 99 µg, P < 0.05) 。右旋美托咪啶組需要止吐治療患者分別為 30%30%10% ,對照組為70%。但四個組中,術後1天和2天病人自控鎮痛嗎啡的需求量並沒有不同。在PACU,術後1天,2天和7天,疼痛評分組間無顯著差異。四組中,後期評分,腸道功能的恢復和出院時間也無顯著差異。

論:術中輔助使用右旋美托咪啶輸注(0.2–0.8 µg · kg–1 · h–1),能減少芬太尼的用量、抗嘔吐治療和在PACU的停留時間 。對後期復蘇(例如,腸功能恢復)或提高病人的整體復蘇品質無顯著作用。當減肥手術中使用右旋美托咪啶推薦輸注率為0.2 µg · kg–1 · h–1,以儘量減少心血管副作用的風險。

(張燕 陳傑 校)

BACKGROUND: Dexmedetomidine (Dex), an {alpha}2 agonist, has well-known anesthetic and analgesic-sparing effects. We designed this prospective, randomized, double-blind, and placebo-controlled dose-ranging study to evaluate the effect of Dex on both early and late recovery after laparoscopic bariatric surgery.

METHODS: Eighty consenting ASA II–III morbidly obese patients were randomly assigned to 1 of 4 treatment groups: (1) control group received a saline infusion during surgery, (2) Dex 0.2 group received an infusion of 0.2 µg · kg–1 · h–1 IV, (3) Dex 0.4 group received an infusion of 0.4 µg · kg–1 · h–1 IV, and (4) Dex 0.8 group received an infusion of 0.8 µg · kg–1 · h–1 IV. Mean arterial blood pressure values were maintained within ±25% of the preinduction baseline values by varying the inspired desflurane concentration. Perioperative hemodynamic variables, postoperative pain scores, and the need for "rescue" analgesics and antiemetics were recorded at specific intervals. Follow-up evaluations were performed on postoperative days (PODs) 1, 2, and 7 to assess severity of pain, analgesic requirements, patient satisfaction with pain management, quality of recovery, as well as resumption of dietary intake and recovery of bowel function.

RESULTS: Dex infusion, 0.2, 0.4, and 0.8 µg · kg–1 · h–1, reduced the average end-tidal desflurane concentration by 19, 20, and 22%, respectively. However, it failed to facilitate a significantly faster emergence from anesthesia. Although the intraoperative hemodynamic values were similar in the four groups, arterial blood pressure values were significantly reduced in the Dex 0.2, 0.4, and 0.8 groups compared with the control group on admission to the postanesthesia care unit (PACU) (P < 0.05). The length of the PACU stay was significantly reduced in the Dex groups (81 ± 31 to 87 ± 24 vs 104 ± 33 min in the control group, P < 0.05). The amount of rescue fentanyl administered in the PACU was significantly less in the Dex 0.2, 0.4, and 0.8 groups versus control group (113 ± 85, 108 ± 67, and 120 ± 78 vs 187 ± 99 µg, respectively, P < 0.05). The percentage of patients requiring antiemetic therapy was also reduced in the Dex groups (30, 30, and 10% vs 70% in the control group). However, the patient-controlled analgesia morphine requirements on PODs 1 and 2 were not different among the four groups. Pain scores in the PACU, and on PODs 1, 2, and 7, in the three Dex groups were not different from the control group. Finally, quality of recovery scores and times to recovery of bowel function and hospital discharge did not differ among the four groups.

CONCLUSIONS: Adjunctive use of an intraoperative Dex infusion (0.2–0.8 µg · kg–1 · h–1) decreased fentanyl use, antiemetic therapy, and the length of stay in the PACU. However, it failed to facilitate late recovery (e.g., bowel function) or improve the patients’ overall quality of recovery. When used during bariatric surgery, a Dex infusion rate of 0.2 µg · kg–1 · h–1 is recommended to minimize the risk of adverse cardiovascular side effects.

 

Rho激酶抑制劑可增強丙泊酚對大鼠支氣管平滑肌收縮的抑制作用

Rho-Kinase Inhibitors Augment the Inhibitory Effect of Propofol on Rat Bronchial Smooth Muscle Contraction

Motohiko Hanazaki, MD*, Masataka Yokoyama, MD*, Kiyoshi Morita, MD*, Atsushi Kohjitani, DDS{dagger}, Hiroyasu Sakai, PhD{ddagger}, Yoshihiko Chiba, PhD{ddagger}, and Miwa Misawa, PhD{ddagger}

From the Departments of *Anesthesiology and Resuscitology, and {dagger}Dental Anesthesiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; and {ddagger}Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.

Anesth Analg 2008 106: 1765-1771.

 

背景:氣管平滑肌收縮不僅由細胞內[Ca2+]增強引起,收縮肌興奮也可增強同一[Ca2+]i的電緊張。小G蛋白RhoRho激酶(ROCK)在Ca2+敏感性調節方面起重要作用。在這項研究中作者研究了三種ROCK抑制劑(fasudil,Y-27632,H-1152)對鼠支氣管平滑肌收縮的效果及ROCK抑制劑對丙泊酚引起的支氣管效應的影響。

方法:雄性Wistar老鼠的肺內支氣管環置於400ul含克-漢二氏溶液的器官浴用劑中,在給予30uM乙醯膽鹼獲得穩定的收縮後,(1)累積使用丙泊酚(1Um -1mM);(2)累積使用Y-276320.01-300uM),法舒地爾(0.01-100uM)或H-11520.01-100 uM);(3)累積共用丙泊酚(1Um-1mM)與Y-27632,法舒地爾或H-11520.03Um0.1uM)。

結果:1)丙泊酚可產生濃度相關的鼠支氣管平滑肌舒張,(2)所有的ROCK抑制劑可產生濃度相關的舒張,(30.03uMY-27632與法舒地爾對丙泊酚的濃度反應曲線沒有明顯影響,而0.1uM時兩種試劑可以使濃度反應曲線明顯左移並降低EC50H-11520.03Um0.1uM)都可明顯使丙泊酚的濃度反應曲線左移並降低EC50

結論:ROCK抑制劑,尤其H-1152能減弱支氣管平滑肌收縮,ROCK抑制劑與丙泊酚合用可產生更明顯的鬆弛作用。

(潘錢玲 陳傑 校)

BACKGROUND: Airway smooth muscle contraction is not caused by the increase in intracellular Ca2+ ([Ca2+]i) alone because agonist stimulation increases tension at the same [Ca2+]i (increase in Ca2+ sensitivity). The small G protein RhoA and Rho-kinase (ROCK) play important roles in the regulation of Ca2+ sensitivity. In this study, we investigated the effects of three ROCK inhibitors (fasudil, Y-27632, and H-1152) on rat airway smooth muscle contraction and the effects of ROCK inhibitors on propofol-induced bronchodilatory effects.

METHODS: Ring strips from intrapulmonary bronchus of male Wistar rats were placed in 400-µL organ baths containing Krebs–Henseleit solution. After obtaining stable contraction with 30 µM acetylcholine, (1) propofol (1 µM–1 mM) was cumulatively applied; (2) cumulative doses of Y-27632 (0.01–300 µM), fasudil (0.01–100 µM), or H-1152 (0.01–100 µM) were applied; (3) propofol (1 µM–1 mM), with Y-27632, fasudil or H-1152 (0.03 µM or 0.1 µM), was cumulatively applied.

RESULTS: (1) Propofol produced concentration-dependent relaxation of rat bronchial smooth muscle. (2) All ROCK inhibitors produced concentration-dependent relaxation. (3) 0.03 µM Y-27632 and fasudil had no significant effect on the concentration–response curve for propofol, while 0.1 µM of both agents significantly shifted concentration–response curves to the left and decreased EC50. H-1152 (both 0.03 µM and 0.1 µM) significantly sifted the concentration–response curve for propofol to the left and decreased EC50.

CONCLUSIONS: ROCK inhibitors, especially H-1152, can attenuate the contraction of rat airway smooth muscle. The combined use of ROCK inhibitors and propofol causes greater relaxation.

 

在七氟醚-氧化亞氮的全身麻醉下剖腹產手術中時BIS值的研究:初產婦和經產婦的比較。

Bispectral Index Values During Sevoflurane-Nitrous Oxide General Anesthesia in Women Undergoing Cesarean Delivery: A Comparison Between Women With and Without Prior Labor

Kyung Y. Yoo, MD, PhD*, Cheol W. Jeong, MD*, Myung W. Kang, MD*, Seok J. Kim, MD*, Sung T. Chung, MD*, Min H. Shin, MD{dagger}, and JongUn Lee, MD, PhD{ddagger}

From the Departments of *Anesthesiology, {dagger}Preventive Medicine, and {ddagger}Physiology, Chonnam National University Medical School, Gwangju, South Korea.

Anesth Analg 2008 106: 1827-1832.

 

背景:選擇性剖腹產手術中呼氣末1%七氟醚與50%氧化亞氮聯合麻醉BIS值>60時,會增加術中知曉風險。作者假設七氟醚-氧化亞氮全身麻醉中經產婦的BIS值比初產婦低。

方法:有40例剖腹產手術的病人參與了本研究。一組是有急診外科手術史的經產婦(經產婦組,n20),另一組是即行手術的初產婦組(對照組,n20)。麻醉誘導用硫噴妥鈉4mg/kg,琥珀膽鹼1.5mg/kg 1 %七氟醚和50 氧化氧氮混合氧氣維持麻醉。評估並比較組間BIS值,收縮壓,心率,血漿應激激素的濃度, Apgar評分及術後鎮痛效果。

結果:在插管和分娩中經產婦的BIS值均較對照組低(p0.001)。兩組患者血漿中去甲腎上腺素濃度均較基礎值增加。經產婦組基礎值和分娩中都比對照組多。收縮壓,心率, Apgar評分,外科手術的特點,和垂體後葉素和皮質醇激素的血漿濃度兩組無顯著差異。兩組術後鎮痛視覺類比評分相似,經產婦組在術後第一個24小時消耗的鎮痛藥較少(p0.01

結論:七氟醚和氧化亞氮全身麻醉下剖腹產手術中經產婦的BIS值比沒有分娩史的初產婦低,且術後鎮痛藥物的消耗量低。

(王騰 陳傑 校)

BACKGROUND: An end-tidal concentration of 1% sevoflurane (1% ETSEVO) in 50% nitrous oxide (N2O) during elective cesarean delivery has been associated with bispectral index (BIS) values >60, which are associated with an increased risk of awareness. We hypothesized that BIS values during sevoflurane-N2O general anesthesia for cesarean delivery would be lower in women with prior labor compared with women without prior labor.

METHODS: Forty patients undergoing cesarean delivery were enrolled in this observational study. One group had urgent surgery after labor (labor group, n = 20) and the other had elective surgery without labor (control group, n = 20). General anesthesia was induced with thiopental 4 mg/kg, followed by succinylcholine 1.5 mg/kg, and maintained with 1% ETSEVO and 50% N2O in oxygen. BIS values, systolic arterial blood pressure, heart rate, plasma stress hormone concentrations, Apgar scores, and postoperative analgesia variables were assessed and compared between groups.

RESULTS: BIS values during the period between intubation and delivery were lower in the labor group than in the control group (P < 0.001). Plasma norepinephrine concentrations increased at delivery compared with baseline in both groups. They were higher in the labor group than in the control group both at baseline and at delivery. Systolic arterial blood pressure, heart rate, Apgar scores, surgical characteristics, and plasma concentrations of vasopressin and cortisol were not different between groups. Postoperative visual analog scale pain scores were similar between groups, while the labor group consumed less analgesics (P < 0.01) during the first 24 h after the operation.

CONCLUSIONS: Prior labor was associated with lower intraoperative BIS values during sevoflurane/N2O general anesthesia and reduced postoperative analgesic consumption in women undergoing cesarean delivery compared with women without prior labor.

 

腹部大手術術後給予氯胺酮可降低嗎啡用量:一項前瞻性、隨機、雙盲、對照研究

Postoperative Ketamine Administration Decreases Morphine Consumption in Major Abdominal Surgery: A Prospective, Randomized, Double-Blind, Controlled Study

Jérome Zakine, MD*, David Samarcq, MD*, Emmanuel Lorne, MD*, Mona Moubarak, MD*, Philippe Montravers, MD, PhD{dagger}, Sadek Beloucif, MD, PhD{ddagger}, and Hervé Dupont, MD, PhD*

From the *Department of Anesthesiology and Critical Care, University Hospital of Amiens, France; {dagger}Department of Anesthesiology and Surgical Critical Care, APHP, Bichat-Claude Bernard University Hospital, Paris, France; and {ddagger}Department of Anesthesiology and Critical Care, APHP, Avicenne University Hospital, Bobigny, France.

Anesth Analg 2008 106: 1856-1861.

 

背景:氯胺酮可降低術後嗎啡用量,但其最佳劑量和持續應用時間仍不清楚。在這項研究中,作者比較術中或術後48小時內給予氯胺酮對嗎啡用量的影響。
方法: 81例接受腹部手術的患者隨機、雙盲分為三組: 1 PERI組術中及術後48小時接受氯胺酮(0.5 mg/kg+2 µg · kg–1 · min–1 ; 2 INTRA組僅術中給予氯胺酮(0.5 mg/kg注射後予2 µg · kg–1 · min–1 ; 3 )對照組給予安慰劑。記錄術後48小時內嗎啡用量,VAS評分及副作用(鎮靜評分,噁心-嘔吐評分,惡夢,精神失常,或幻想)。

結果:術後24小時嗎啡累積用量PERI(中位數 = 27 mg, 離散度= [19])顯著低於INTRA(48 mg [41.5])和對照組(50 mg [21]) (P < 0.005)PERI組和INTRAVAS評分均明顯低於對照組( P < 0.001 ), 對照組與PERI組相比噁心發生較高27 %與4 P= 0.005 。各組間鎮靜評分和精神失常無差別。
結論:術後48小時內給予小劑量氯胺酮可改善術後鎮痛效果顯著降低嗎啡用量,而且噁心發生率較低並無副作用。

(陳偉 陳傑 校)

BACKGROUND: Ketamine decreases postoperative morphine consumption, but its optimal dosing and duration of administration remain unclear. In this study, we compared the effects of ketamine administration on morphine consumption limited to the intraoperative period, or continued for 48 h postoperatively.

METHODS: Eighty-one patients scheduled for abdominal surgery were prospectively randomized under double-blind conditions to three groups: (1) PERI group receiving intraoperative and postoperative ketamine for the first 48 h after surgery (2 µg · kg–1 · min–1 after a 0.5 mg/kg bolus); (2) INTRA group receiving intraoperative ketamine administration only (2 µg · kg–1 · min–1 after a 0.5 mg/kg bolus); and (3) CTRL group receiving placebo. Morphine consumption, visual analog scale scores and side effects (sedation score, nausea-vomiting score, nightmares, psychiatric disorders, or delusions) were recorded for the first 48 h.

RESULTS: Cumulative morphine consumption 24 h after surgery was significantly lower in the PERI group (median = 27 mg, interquartile range = [19]) than in the INTRA group (48 mg [41.5]) and CTRL group (50 mg [21]) (P < 0.005). Postoperative visual analog scale scores were significantly lower in the PERI group and INTRA group than in the CTRL group (P < 0.001). A higher rate of nausea was observed in the CTRL group compared with the PERI group (27% vs 4%, P = 0.005). No difference in sedation scores or psychiatric disorders was observed among groups.

CONCLUSIONS: Low-dose ketamine improved postoperative analgesia with a significant decrease of morphine consumption when its administration was continued for 48 h postoperatively, with a lower incidence of nausea and with no side effects of ketamine.

 

圍術期使用加巴噴丁對整形外科病人鞘內注射嗎啡引起的術後瘙癢症的保護作用

Preoperative Gabapentin Prevents Intrathecal Morphine-Induced Pruritus After Orthopedic Surgery

Michael J. Sheen, MD*, Shung-Tai Ho, MD, MS*, Chian-Her Lee, MD{dagger}, Yu-Chi Tsung, MD*, and Fang-Lin Chang, MD*

From the Departments of *Anesthesiology and {dagger}Orthopedic Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Anesth Analg 2008 106: 1868-1872.

 

背景:瘙癢是鞘內注射嗎啡最常見的副作用。加巴噴丁是一種抗驚厥藥,並且已經被證實對某些慢性瘙癢有一定的治療作用。但是它用於鞘內注射嗎啡引起的瘙癢的療效還未進行評估。

方法:86名脊髓麻醉下行下肢手術的病人隨機、雙盲分為兩組,術前2小時分別給予1200mg的加巴噴丁或安慰劑。所有的病人都鞘內注射0.5%的布比卡因15mg和嗎啡0.2mg。在鞘內注射嗎啡後3691224h觀察是否發生瘙癢。

結果:對照組較加巴噴丁組出現瘙癢的病人多(77.5%vs47.5%P=0.01)。加巴噴丁組患者發生瘙癢的時間較對照組患者推遲。鞘內注射嗎啡3h6h後瘙癢的嚴重程度試驗組較輕。

結論:術前給加巴噴丁能防止下肢手術病人鞘內注射嗎啡引起的瘙癢。

(王鵬 陳傑 校)

BACKGROUND: Pruritus is the most common side effect of intrathecal morphine. Gabapentin is an anticonvulsant and had been reported to be effective in some chronic pruritus conditions. Its effect in intrathecal morphine-induced pruritus has not yet undergone an evaluation.

METHODS: We randomly allocated 86 patients scheduled for lower limb surgery under spinal anesthesia into two equal groups that received either gabapentin 1200 mg or placebo 2 h before operation in a prospective, double-blind manner. All patients received an intrathecal injection of 15 mg of 0.5% isobaric bupivacaine and 0.2 mg preservative-free morphine. Pruritus was evaluated at 3, 6, 9, 12, and 24 h after intrathecal morphine administration.

RESULTS: The incidence of pruritus was significantly more frequent in the placebo group compared with the gabapentin group (77.5% vs 47.5%; P = 0.01). The onset time of pruritus in the gabapentin group (6.2 ± 1.8 h) was significantly delayed compared with that in the placebo group (3.1 ± 0.8 h) (P < 0.0001). The severity of pruritus was significantly more in the placebo group compared with the gabapentin group at 3 and 6 h after intrathecal morphine injection.

CONCLUSION: Preoperative gabapentin prevents pruritus induced by intrathecal morphine in patients undergoing lower limb surgery with spinal anesthesia.

 

大鼠脊髓腰段腺苷A2A受體的表達及對NMDA受體離子流的調節作用

Expression of Adenosine A2A Receptors in the Rat Lumbar Spinal Cord and Implications in the Modulation of N-Methyl-d-Aspartate Receptor Currents

Emmanuel Guntz, MD*{dagger}, Hélène Dumont, MD*{dagger}, Els Pastijn, MD*{dagger}, Alban de Kerchove d’Exaerde, PhD{dagger}, Karima Azdad, PhD{dagger}, Maurice Sosnowski, MD, PhD*{dagger}, Serge N. Schiffmann, MD, PhD{dagger}, and David Gall, PhD{dagger}

From the *Department of Anesthesiology, Hôpital Universitaire Saint-Pierre, and {dagger}Laboratory of Neurophysiology, Université Libre de Bruxelles, Brussels, Belgium.

.Anesth Analg 2008 106: 1882-1889.

 

背景:脊髓背角A2A受體的存在仍然有爭論。該水準的NMDA受體啟動後興奮性增強,臨床上表現為痛覺過敏。已有研究顯示大鼠紋狀體神經元A2A受體啟動後抑制NMDA受體的離子流。在本研究中,作者在大鼠脊髓腰段背角第二薄層神經元內尋找腺苷A2A受體,並研究A2A受體啟動後能否調節NMDA受體的離子流。

方法:試驗在大鼠脊髓腰段進行。脊髓腰段內的腺苷A2A受體轉錄體通過RT-PCR技術測定。同時也做Western blot試驗。RT-PCR技術還專門用於第二薄層,且第二薄層神經元內腺苷A2A受體轉錄體通過單細胞RT-PCR技術檢測。腺苷A2A受體啟動後對NMDA受體的作用通過全細胞結構膜片鉗技術研究。

結果 RT-PCR顯示在脊髓腰段存在腺苷A2A受體轉錄體。Western blot試驗揭示了A2A受體存在于脊髓腰段。在脊髓膠質進行的RT-PCR也顯示了腺苷A2A受體轉錄體的存在。最後,單細胞RT-PCR也顯示腺苷A2A受體轉錄體存在于第二薄層神經元的標本中。膜片鉗的結果表明應用選擇性A2A受體激動劑可抑制NMDA受體的離子流。

結論:這些結果證明A2A受體存在於大鼠脊髓腰段背角膠質的神經元內,並且通過應用選擇性A2A受體激動劑抑制NMDA介導的離子流。因此,A2A受體的配體能夠調節在脊髓水準的疼痛傳導過程。

(趙燕星 陳傑 校)

BACKGROUND: The presence of A2A receptors in the dorsal horn of the spinal cord remains controversial. At this level, activation of N-methyl-d-aspartate (NMDA) receptors induces wind-up, which is clinically expressed as hyperalgesia. Inhibition of NMDA receptor currents after activation of A2A receptors has been shown in rat neostriatal neurons. In this study, we sought to establish the presence of adenosine A2A receptors in the lamina II of the rat lumbar dorsal horn neurons and investigated whether the activation of A2A receptors is able to modulate NMDA receptor currents.

METHODS: Experiments were conducted in the rat lumbar spinal cord. The presence of adenosine A2A receptor transcripts inside the lumbar spinal cord is assessed with the reverse transcriptase polymerase chain reaction (RT-PCR) technique. Western blot experiments are performed at the same level. The RT-PCR technique is also performed specifically in the lamina II, and the presence of adenosine A2A receptor transcripts is assessed in neurons from the lamina II with the single-cell RT-PCR technique. The effect of adenosine A2A receptor activation on NMDA receptor currents is studied by the whole-cell configuration of the patch clamp technique.

RESULTS: RT-PCR performed on the lumbar spinal cord revealed the presence of adenosine A2A receptor transcripts. Western blot experiments revealed the presence of A2A receptors in the lumbar spinal cord. RT-PCR performed on the substantia gelatinosa also revealed the presence of adenosine A2A receptor transcripts. Finally, single cell RT-PCR revealed the presence of adenosine A2A receptor transcripts in a sample of lamina II neurons. Patch clamp recordings showed an inhibition of NMDA currents during the application of a selective A2A agonist.

CONCLUSIONS: These results demonstrate the presence of A2A receptor on neurons from the substantia gelatinosa of the rat lumbar dorsal horn and the inhibition of NMDA-induced currents by the application of a selective A2A receptor agonist. Therefore, A2A receptor ligands could modulate pain processing at the spinal cord level.

 

伏核內多巴胺D2樣受體與氧化亞氮(N2O)的鎮痛作用

Dopamine D2-Like Receptor in the Nucleus Accumbens Is Involved in the Antinociceptive Effect of Nitrous Oxide

Sahoko Koyanagi, MD*, Shugaku Himukashi, MD*, Kumiko Mukaida, MD*, Tsutomu Shichino, MD{dagger}, and Kazuhiko Fukuda, MD*

From the *Department of Anesthesia, Kyoto University Hospital, and {dagger}National Hospital Organization Kyoto Medical Center, Kyoto, Japan.

Anesth Analg 2008 106: 1904-1909.

 

背景:N2O的抗傷害機制還未完全闡明。另一方面,許多研究表明與記憶及強化過程有關的中腦邊緣系統多巴胺能神經元在脊神經索鎮痛系統中有重要作用。作者假設中腦邊緣多巴胺能系統與N2O的抗傷害作用有關。

方法:本研究應用成年雄性Fischer大鼠。為了檢測多巴胺能系統是否是由N2O啟動的,暴露於75%N2O的大鼠腦腹側被蓋區冰凍切片用雙重染色的方法來檢測c-Fos與酪氨酸羥化酶。為了鑒定多巴胺能系統是否與N2O的抗傷害作用有關,應用生理鹽水或雷氯必利(多巴胺D2樣受體拮抗劑)注射到伏核殼(NAc)區域。在暴露於25%氧氣75%氮氣或25%氧氣75%N2O30min後大鼠接受福馬林試驗,並用免疫組化方法檢測其脊髓。

結果:暴露于75%N2O增加腦腹側被蓋區酪氨酸羥化酶陽性細胞內c-Fos表達。福馬林試驗顯示伏核殼(NAc)區注射雷氯必利減弱了N2O的抗傷害作用,且阻斷了N2O對脊髓背角福馬林誘導的c-Fos表達的抑制作用。

結論:吸入N2O可能啟動中腦邊緣多巴胺能神經元,而且N2O的抗傷害作用至少部分是由伏核殼(NAc)區域的多巴胺D2樣受體介導的。

(張江玲 陳傑 校)

BACKGROUND: The mechanism of the antinociceptive effects of nitrous oxide (N2O) has not been completely elucidated. On the other hand, numerous studies have indicated that mesolimbic dopaminergic neurons, which are thought to be involved in rewarding and reinforcement processes, play important roles in the supraspinal pain-suppression system. We hypothesized that the mesolimbic dopaminergic system is involved in the antinociceptive effect of N2O.

METHODS: Adult male Fischer rats were used in this study. To examine whether the dopaminergic system is activated by N2O, frozen sections of the ventral tegmental area of rats exposed to 75% N2O were double-stained for c-Fos and tyrosine hydroxylase. To clarify whether the dopaminergic system is involved in the antinociceptive action of N2O, saline or raclopride, a dopamine D2-like receptor antagonist, was injected into the nucleus accumbens (NAc) shell region. After exposure to 25% oxygen–75% nitrogen or 25% oxygen–75% N2O for 30 min, rats were subjected to formalin test, and the spinal cord was examined immunohistochemically.

RESULTS: Exposure to 75% N2O increased c-Fos expression in tyrosine hydroxylase-positive cells in the ventral tegmental area. Raclopride, injected into the NAc shell region, attenuated the antinociceptive effect of N2O in the formalin test, and blocked the suppressive effect of N2O on the formalin-induced c-Fos expression in the dorsal horn of the spinal cord by N2O.

CONCLUSION: It is possible that inhalation of N2O activates mesolimbic dopaminergic neurons, and that the antinociceptive effect of N2O is at least partially mediated by dopamine D2-like receptors in the NAc shell region.

 

經皮吹入氧氣並不能改善心臟手術病人胸骨傷口的氧合

Transdermal Oxygen Does Not Improve Sternal Wound Oxygenation in Patients Recovering from Cardiac Surgery

Mohamed H. Bakri, MD, PhD*, Hassan Nagem, MD*, Daniel I. Sessler, MD*, Ramatia Mahboobi, MD*, Jarrod Dalton, MA*{dagger}, Ozan Akça, MD{ddagger}§, Eric E. Roselli, MD||, and Steven R. Insler, DO

From the Departments of *Outcomes Research, {dagger}Quantitative Health Sciences, ||Cardiothoracic Surgery, and ¶Cardiothoracic Anesthesia, The Cleveland Clinic, Cleveland, Ohio; {ddagger}Department of Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, Kentucky; and §Outcomes Research Consortium.

.Anesth Analg 2008 106: 1619-1626.

 

背景:心外科手術中,胸骨傷口裂開和感染的發生率為1%。組織氧壓(PsqO2)是術後感染的主要危險因素,傷口裂開患者的的組織氧壓一般較低。我們研究該假設,在心外科手術病人中經皮供氧是否可以改善胸骨傷口的氧合。我們的第二個假設是,額外吸氧是否可以改善傷口的PsqO2

方法:心肺分流術後,30名患者隨機分組,接受治療(12 EpiFlo 氧發生機(Ogenix, Inc., Beachwood, OH)6 mL/h向封閉的包裹傷口內供氧或(2)不給予上述治療。測定傷口下{approx}5 mm處的 PsqO2 和溫度。在給予氧療(Fio2 = 60%)1h 測定PsqO2 和動脈氧分壓 (Pao2),在監護室的第一天和第二天早上隨機分兩組供氧,Fio2 分別為30%50%

結果:由於技術問題,4名病人出組。病人的基本情況、手術類型和圍手術期處理在各組基本一致。增加Fio2 30% 50% 可以改善 Pao2 99 [84–116]149 [128–174] mm Hg (P < 0.001, mean [95% CI]) ,胸骨傷口的 PsqO223 [16–33]27 [19–38] mm Hg (P < 0.001).相比較,局部吹入氧氣,組織的氧合沒有明顯改善:前後分別為24 [14–41] 25 [16–41] mm Hg (P = 0.88)

結論:額外的增加吸入氧氣可以改善心肺分流術後Pao2和胸骨PsqO2 ,從而降低感染的風險。然而,向封閉的包裹傷口內供氧並不能有效改善傷口 PsqO2 ,因而並不能有效降低心臟手術後胸骨傷口處的感染。

(章一靜譯,薛張綱校)

BACKGROUND: Sternal wound dehiscence and infection complicate 1% of cardiac surgeries. Tissue oxygen tension (PsqO2) is the primary determinant of surgical wound infection risk and is often critically low in surgical incisions. We tested the hypothesis that local transdermal delivery of oxygen improves oxygenation in sternotomy wounds after cardiac surgery. Our secondary hypothesis was that supplemental inspired oxygen improves sternal wound PsqO2.

METHODS: After undergoing cardiopulmonary bypass, 30 patients randomly received (1) 2 EpiFlo oxygen generators (Ogenix, Inc., Beachwood, OH) that provided oxygen at 6 mL/h into an occlusive wound dressing or (2) identical-appearing inactive generators. PsqO2 and temperature were measured in the wound {approx}5 mm below the skin surface. PsqO2 and arterial oxygen (Pao2) were measured 1 h after intensive care unit admission (Fio2 = 60%) and on the first and second postoperative mornings at Fio2 of both 30% and 50% in random order.

RESULTS: Data from four patients were excluded for technical reasons. Patient characteristics were similar in each group, as were type of surgery and perioperative management. Increasing Fio2 from 30% to 50% improved Pao2 from 99 [84–116] to 149 [128–174] mm Hg (P < 0.001, mean [95% CI]) and sternal wound PsqO2 from 23 [16–33] to 27 [19–38] mm Hg (P < 0.001). In contrast, local oxygen delivery did not improve tissue oxygenation: 24 [14–41] vs 25 [16–41] mm Hg (P = 0.88).

CONCLUSIONS: Additional inspired oxygen improved Pao2 and sternal wound PsqO2 after bypass and may, consequently, reduce infection risk. However, oxygen insufflated locally into an occlusive dressing did not improve wound PsqO2 and, therefore, does not appear to be useful clinically in cardiac surgery patients to reduce sternal wound infections.

 

 

對新生兒大腦的神經保護對策

Neuroprotective Strategies for the Neonatal Brain

Degos, Vincent MD*†; Loron, Gauthier MD*†; Mantz, Jean MD, PhD*†‡; Gressens, Pierre MD, PhD*†§

From the *Inserm, U676, Paris, France; {dagger}Université Paris 7, Faculté de Médecine Denis Diderot, IFR02 and IFR25, Paris, France; {ddagger}AP HP, Hôpital Beaujon, Département d’Anesthésie Réanimation, Clichy, France; and §AP HP, Hôpital Robert Debré, Service de Neurologie Pédiatrique, Paris, France.

Anesth Analg 2008 106: 1670-1680.

 

圍產期大腦的損傷是兒童時期死亡和終生殘廢的首要原因。腦性麻痹和認知缺損通常是由於室周圍白質損害,主要見於32周胎齡前出生的嬰兒;而皮層皮層下的損害主要發生于足月兒。雖然近來在新生兒監護方面有所進步,但是對圍產期的腦損傷仍沒有有效的治療方法。幾種干預措施,例如硫酸鎂用於早產新生兒,低體溫用於足月兒,是已完成的或正在進行中的臨床試驗的焦點。正如這篇綜述所討論的,對圍產期大腦損傷的病理生理學機制的改良認識有助於識別神經保護干預措施的潛在的靶位。

(宣麗真譯 薛張綱校)

Injury to the perinatal brain is a leading cause of childhood mortality and lifelong disability. Cerebral palsy and cognitive impairment are usually related to periventricular white matter damage, which is seen chiefly in babies born before 32 wk gestational age, and to corticosubcortical lesions, which occur mainly in full-term infants. Despite recent improvements in neonatal care, no effective treatment for perinatal brain lesions is available. Several interventions, such as magnesium sulfate in preterm newborns and hypothermia in term newborns, are the focus of completed or continuing clinical trials. Improved understanding of the pathophysiological mechanisms involved in perinatal brain lesions helps to identify potential targets for neuroprotective interventions, as discussed in this review.

 

 

小計量異丙酚引起乳鼠大腦神經元凋亡

Subanesthetic Doses of Propofol Induce Neuroapoptosis in the Infant Mouse Brain

Davide Cattano, MD, PhD*{dagger}, Chainllie Young, MD, PhD{ddagger}, Megan M.W. Straiko, PhD{ddagger}, and John W. Olney, MD{ddagger}

From the *Department of Anesthesiology, WA University School of Medicine, Saint Louis, Missouri; {dagger}Department of Surgery, University of Pisa, School of Medicine, Pisa, Italy; and {ddagger}Department of Psychiatry, WA University School of Medicine, Saint Louis, Missouri.

Anesth Analg 2008 106: 1712-1714.

 

可阻斷NMDA受體或者激動GABA-A抑制受體的藥物具有引起發育中齧齒動物大腦神經元凋亡的作用。異丙酚曾被報導對上述兩者均有影響,但並未充分證實可引起發育中的神經元凋亡。我們假定滿足一隻乳鼠接受外科手術麻醉的腹膜內給藥劑量是200 mg/kg。然後我們將異丙酚劑量進行分級(25–300 mg/kg i.p.),發現≥50 mg/kg的劑量可引起顯著的神經元凋亡。由此我們得出結論,1/4手術麻醉劑量的異丙酚即可引起乳鼠大腦神經元凋亡。

(夏俊明譯 薛張綱校)

Drugs that block N-methyl-d-aspartate glutamate receptors or that promote {gamma}-aminobutyric acid type A inhibition trigger neuroapoptosis in the developing rodent brain. Propofol reportedly interacts with both {gamma}-aminobutyric acid type A and N-methyl-d-aspartate glutamate receptors, but has not been adequately evaluated for its ability to induce developmental neuroapoptosis. Here we determined that the intraperitoneal (i.p.) dose of propofol required to induce a surgical plane of anesthesia in the infant mouse is 200 mg/kg. We then administered graduated doses of propofol (25–300 mg/kg i.p.) and found that doses ≥50 mg/kg induce a significant neuroapoptosis response. We conclude that propofol induces neuroapoptosis at 1/4 the dose required for surgical anesthesia.

 

術前口服Passiflora減輕門診病人的焦慮:一項雙盲,安慰劑控制的研究

Preoperative Oral Passiflora Incarnata Reduces Anxiety in Ambulatory Surgery Patients: A Double-Blind, Placebo-Controlled Study

Ali Movafegh, MD*, Reza Alizadeh, MD{dagger}, Fatimah Hajimohamadi, MD{ddagger}, Fatimah Esfehani, MD{dagger}, and Mohmad Nejatfar, MD{dagger}

From the *Department of Anesthesiology and Critical Care, {dagger}Research Development Center, Dr Ali Shariati Hospital, and {ddagger}Department of Anesthesiology and Critical Care, Amir Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran.

.Anesth Analg 2008; 106:1728-1732

 

背景:許多術前手術的病人有焦慮症狀,因此研究一種術前使用的能減輕焦慮而又對精神運動損傷最輕的藥物是很必要的。

方法:在該研究中60名研究物件被隨機等分成兩組,分別於術前90分鐘口服西番蓮屬翹搖苷(500 mg, PassipyTM IranDarouk)和安慰劑。於服藥前,服藥後10, 30, 60,90分鐘都對每名患者的焦慮和鎮靜狀態予以評估,該評估以量化測試的方式進行。在病人進入手術室,拔管後3090分鐘對精神狀態予以評估,該評估採用Trieger Dot 測試和Digit-Symbol 替代測試。每名患者從進入PACU到離開的時間間隔被記錄下來。

結果:兩組病人的人口統計學特徵,ASA分級,手術時間,基礎NRS評分,在預設時間內的鎮靜狀態,離開時間都差不多。口服西番蓮屬組的NRS焦慮評分明顯低於對照組(P < 0.001)。兩組在PACU裏的心理狀態和精神運動功能恢復情況沒有太大差別。

結論:門診手術的病人術前口服西番蓮屬可以減輕焦慮而不產生過度鎮

(孫鵬飛譯 薛張綱校)

BACKGROUND: Many patients have preoperative anxiety; therefore, the development of a strong anxiolytic with minimal psychomotor impairment for premedication may be desirable.

METHODS: In this study, 60 patients were randomized into two groups to receive either oral Passiflora incarnata (500 mg, PassipyTM IranDarouk) (n = 30) or placebo (n = 30) as premedication, 90 min before surgery. A numerical rating scale (NRS) was used for each patient to assess anxiety and sedation before, and 10, 30, 60, and 90 min after premedication. Psychomotor function was assessed with the Trieger Dot Test and the Digit-Symbol Substitution Test at arrival in the operating room, 30 and 90 min after tracheal extubation. The time interval between arrival in the postanesthesia care unit and discharge to home (discharge time) was recorded for each patient.

RESULTS: The demographic characteristics of patients, ASA physical status, duration of surgery, basal NRS score, sedation at the preset time intervals, and discharge time were similar in the two groups. The NRS anxiety scores were significantly lower in the passiflora group than in the control group (P < 0.001). There were no significant differences in psychological variables in the postanesthesia care unit and recovery of psychomotor function was comparable in both groups.

CONCLUSIONS: In outpatient surgery, administration of oralPassiflora incarnata as a premedication reduces anxiety without inducing sedation.

 

 

在人低劑量吸入七氟醚後可以減少粒細胞-血小板的聚集作用

Delayed Inhibition of Agonist-Induced Granulocyte-Platelet Aggregation After Low-Dose Sevoflurane Inhalation in Humans

Johannes Wacker, MD*, Eliana Lucchinetti, PhD{ddagger}, Marina Jamnicki, MD*, José Aguirre, MD*, Luc Härter, PhD{dagger}, Marius Keel, MD{dagger}, and Michael Zaugg, MD{ddagger}

From the *Institute of Anesthesiology, {dagger}Department of Trauma Surgery, and {ddagger}Cardiovascular Anesthesia Research Laboratory, Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland.

Anesth Analg 2008 106: 1749-1758.

 

背景:七氟醚是有內皮保護作用的鎮靜鎮痛的藥物,我們在人體試驗了吸入低劑量的七氟醚是否可以持續抑制粒細胞-血小板啟動的副作用。

方法:10名健康的成年男性志願者參與了這項研究。每人吸入 0.5–1 %的七氟醚1h,吸入氧濃度為50 vol %。單純吸入50%額氧氣為對照組。 分別在試驗前、吸入七氟醚即刻、吸入七氟醚24h三個時間點抽取靜脈血,通過流式細胞儀測定粒細胞和血小板表面分子標誌物 (CD41, CD42b, CD62P/P-selectin, and PAC-1),通過血栓彈力圖評估白陶土誘導的血栓形成。在流式細胞儀的試驗中,血小板被花生四膝酸(AA, 30 µM),氯喹腺苷 (ADP, 1 µM)和凝血酶受體激肽(TRAP-6, 6 µM)刺激。

結果:AA, ADP,TRAP-6增加了血小板CD42b的表達,而CD62PPAC-1的表達下降。受到刺激,粒細胞和血小板的聚集增加。相比於對照組,低劑量的吸入七氟醚24h後可以降低 ADP誘導的血小板CD62P 的表達,在124h後減少因AAADP刺激引起的粒細胞-血小板聚集物的形成,以及在24h後減少TRAP-6的這個作用。 相比於對照組,吸入七氟醚24h後減少粒細胞-血小板聚集物的形成以及減少伴隨的血凝塊形成的作用持續存在。

結論:我們在第一時間證明了,低劑量的吸入七氟醚(<1 %)後24h可以減少粒細胞-血小板的啟動以及伴隨的血栓和形成。

(施穎譯,薛張綱校)

BACKGROUND: Sevoflurane can be used as sedative-analgesic drug with endothelial protective properties. We tested whether low-dose sevoflurane inhalation provides sustained inhibition of detrimental granulocyte-platelet aggregation in humans.

METHODS: Ten healthy male volunteers were enrolled in this crossover study. Each subject inhaled sevoflurane for 1 h at 0.5–1 vol % end-tidal concentration in oxygen (50 vol %). Inhaling oxygen (50 vol %) alone served as control. Venous blood samples were collected at baseline before inhalation, immediately after inhalation, and 24 h thereafter, and were used for flow cytometry to determine platelet surface marker (CD41, CD42b, CD62P/P-selectin, and PAC-1) on platelets and granulocytes and for kaolin-induced clot formation, as assessed by thromboelastography. In flow cytometry experiments, platelets were stimulated with arachidonic acid (AA, 30 µM), adenosine diphosphate (ADP, 1 µM), and thrombin receptor agonist peptide-6 (TRAP-6, 6 µM).

RESULTS: AA, ADP, and TRAP-6 markedly increased the expression of CD62P on platelets, whereas CD42b (shedding) and PAC-1 (heterotypic conjugates) expression decreased. The amount of granulocyte-platelet aggregates increased upon agonist stimulation. Low-dose sevoflurane inhalation reduced ADP-induced CD62P expression on platelets 24 h after inhalation, and inhibited the formation of granulocyte-platelet aggregates under stimulation with AA and ADP after 1 and 24 h, and with TRAP-6 after 24 h compared with control. Inhibition of granulocyte-platelet aggregates was accompanied by reduced clot firmness 24 h after sevoflurane inhalation compared with control.

CONCLUSIONS: We demonstrated for the first time that inhaling low-dose sevoflurane (<1 vol % end-tidal) inhibits agonist-induced granulocyte-platelet interactions 24 h after administration and thus counteracts thromboin flammatory processes.

 

 

延長使用異氟醚、丙泊酚、右旋美托咪定、氯胺酮對於成年鼠神經細胞增殖的影響

The Effect of Prolonged Anesthesia with Isoflurane, Propofol, Dexmedetomidine, or Ketamine on Neural Cell Proliferation in the Adult Rat

Tung, Avery MD*; Herrera, Stacy BS*; Fornal, Casimir A. PhD; Jacobs, Barry L. PhD

From the *Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois; {dagger}Program in Neuroscience, Princeton University, Princeton, New Jersey.

Anesth Analg 2008 106: 1772-1777

 

背景:最近有證據表明,成年動物海馬區新神經元的增殖對於學習、記憶等認知功能有著重要作用。在動物個體中,神經元的增殖受著年齡增長、GABA受體活動、基底前腦電活動、腦組織去甲腎上腺素水準降低、環境刺激減弱這些因素的抑制。這些情況與麻醉過程的相似提示我們,麻醉過程可能會調整新細胞的增殖,甚至由麻醉引起的成年動物神經細胞生長抑制會引起術後認知功能障礙。為了檢驗這種假設,我們研究了四種麻醉藥物的延長麻醉對於年幼及年長大鼠的海馬區神經細胞增殖的影響。

方法:年幼(約3月齡)以及年長(約12月齡)的雄性Sprague-Dawley鼠,用四種(異氟醚、丙泊酚、右旋美托咪定、氯胺酮)之一的麻醉劑麻醉8小時,大鼠採用自主呼吸,麻醉劑的濃度以正向反射消失以及能耐受夾式血氧檢測儀來滴定。暴露于麻醉劑6個小時時,給予大鼠腹腔內注射200mg/kg的溴去氧尿苷(bromodeoxyuridine,BrdU),數小時後處死。收集其海馬部位的冰凍切片,使用免疫酶標技術來測定其BrdU濃度,計數齒狀回的BrdU陽性細胞數,並與未麻醉的對照組相比較,以此給細胞增殖分級。年幼大鼠組四種麻醉劑都使用。年長大鼠只使用異氟醚和氯胺酮,並且在晚上吸入異氟醚。

結果:共有年幼大鼠42只,中年及老年大鼠26只參加實驗。與對照組相比,年幼大鼠中使用任一麻醉劑的延長麻醉對於BrdU陽性細胞計數並無影響。年長大鼠中,在白天吸入異氟醚8小時對於BrdU標記亦沒有影響。年長鼠與年幼鼠相比較,BrdU陽性細胞數顯著較高。年長鼠中,氯胺酮麻醉者與對照組相比較,BrdU陽性細胞數降低26%。年長鼠在晚上吸入異氟醚8小時者與未麻醉的對照組相比,BrdU標記並無明顯差異。

結論:即使使用了多種的、不同的麻醉藥物,我們發現延長麻醉對於年幼大鼠的海馬區細胞增殖並沒有什麼影響;而氯胺酮麻醉對於年長鼠的海馬區細胞增殖有輕微的抑制作用,且異氟醚麻醉並未發現晝夜節律影響。這些資料都表明,麻醉劑似乎並不能影響神經細胞的增殖。更進一步的說,麻醉劑誘發的細胞增殖抑制作用在術後認知功能障礙中並不是主要角色。對比思考我們的實驗發現,以及現有的對於麻醉劑作用過程的理解,和已知的細胞增殖修飾基因的瞭解,我們得到了一個並不完整的認識,來解釋究竟是什麼因素在神經元細胞的增殖中起了藥理學和行為學層面的關鍵作用。

(秦敏菊譯 薛張綱校)

BACKGROUND: Recent evidence indicates that new neurons are produced in the adult hippocampus, and play a functional role in cognitive processes such as learning and memory. In animals, new neuron production is suppressed by increasing age, [gamma]-aminobutyric acid receptor activity, reductions in basal forebrain activity and brain norepinephrine levels, and decreased environmental stimuli. Similarities between these effects and those of anesthetic administration suggest that anesthetics may modulate new cell production, and raise the possibility that postoperative cognitive dysfunction may result, in part, from anesthetic-induced suppression of adult neurogenesis. To test this hypothesis, we investigated the effects of prolonged anesthesia with four different anesthetics on hippocampal cell proliferation in young and older rats.

METHODS: Young (approximately 3 mo) and older, middle-aged (approximately 12 mo) male Sprague-Dawley rats received one of four anesthetics (propofol, isoflurane, dexmedetomidine, and ketamine) for 8 h. Rats breathed spontaneously, and anesthesia was titrated to loss of righting reflex and tolerance of clip-style pulse oximetry. Six hours into the anesthetic, rats received 200 mg/kg bromodeoxyuridine (BrdU) intraperitoneally and were killed hours later. Frozen hippocampal sections were collected and processed for BrdU using an immunoperoxidase technique. BrdU(+) cells in the dentate gyrus were then counted, and compared with unanesthetized controls to determine the degree of new cell production. All four anesthetics were given to young rats. Older rats received isoflurane and ketamine, and also received isoflurane during their dark phase.

RESULTS: Forty-two young, and 26 older, middle-aged rats were studied. When compared with controls, prolonged anesthesia in young rats with any drug had no effect on the number of BrdU(+) cells. BrdU labeling was also unaffected in older rats given isoflurane for 8 h during the light phase. Older rats had significantly lower BrdU(+) cell counts than younger rats. In older rats, ketamine anesthesia reduced BrdU(+) cell counts by 26% when compared with unanesthetized controls. Older rats given isoflurane for 8 h during their dark phase demonstrated no difference in BrdU labeling when compared with unanesthetized controls.

CONCLUSION: Despite using multiple, mechanistically distinct drugs, we found no effect of prolonged anesthesia on adult hippocampal cell proliferation in young rats, a slight suppressive effect of ketamine in older rats, and no circadian effect with isoflurane. These data indicate that anesthetics are unlikely to alter cell proliferation, and by extension that anesthetic-induced inhibition of cell proliferation is unlikely to play a major role in postoperative cognitive impairment. The contrast between our findings, current concepts of anesthetic action, and known modifiers of cell proliferation suggest an incomplete understanding of the pharmacological and behavioral factors governing new neuron production.

 

 

評判手術病人外周血細胞比容的應用:不能很好反映真實血細胞容量

Peripheral Blood Hematocrit in Critically Ill Surgical Patients: An Imprecise Surrogate of True Red Blood Cell Volume
Danny M. Takanishi, Mihae Yu, Fedor Lurie, Elisabeth Biuk-Aghai, Hideko Yamauchi, Hao Chih Ho, and Alyssa D. Chapital

From the Divisions of Surgical Critical Care and Trauma, Department of Surgery, John A. Burns School of Medicine, University of Hawaii and The Queen’s Medical Center, Honolulu, Hawaii.

.Anesth Analg 2008 106: 1808-1812.

 

背景:外周血細胞比容一般被用來作為是否輸血的指標。但對於手術病人來說,改指標並不能有效反映真實的紅細胞含量。我們比較了外周血細胞比容與以下三方面的關係:(1)血漿容量,(2)估計迴圈血容量,(3)標化的血細胞比容與它們的關係。

方法:我們使用了BVA-100血容量分析儀(Daxor Corporation, New York City, NY)評估了入外科監護室的病人的情況。血漿容量直接通過連續標記白蛋白濃度來測定。紅細胞容量通過血漿容量和外周紅細胞比容計算而得。所有容量指標使用標化百分比含量表示。通過Metropolitan壽命表中的理想體重經公式計算得到理想容量。外周血細胞比容與標化的血細胞比容相比較,從而判斷該指標是否可以反映正常的血容量

結果:從40名平均年齡在61 ± 20歲的病人處獲得了86個資料,這些病人的ASA評分II級得分20 ± 6,死亡率為13%。入院的主要原因是嚴重的敗血症 (n = 11),出血性休克(n = 7),呼吸衰竭(n = 20)和心臟衰竭(n = 2)Bland–Altman分析顯示標準和外周血細胞比容的平均差值是3.4 ± 7.895%的置信區間是1.7–5.148%的外周血細胞比容低於標化血細胞比容 17%的外周血細胞比容高於標化血細胞比容,兩者一致的為 35%

結論:外周血細胞比容可能不能準確得反映手術病人血細胞含量。這個結論需要更大樣本的手術病人通過比較雙重同位素技術來驗證。

(劉婷潔譯,薛張剛校)
BACKGROUND: Peripheral blood hematocrit (red blood cell volume/total blood volume) is conventionally used to determine the need for blood transfusions. In critically ill surgical patients, this variable may not accurately approximate true red blood cell volume. We compared peripheral blood hematocrit to (1) plasma volume, (2) estimated circulating blood volume, and (3) a normalized hematocrit to clarify their relationships.

METHODS: Consecutive patients admitted to the surgical intensive care unit were evaluated using the BVA-100 Blood Volume Analyzer (Daxor Corporation, New York City, NY). Plasma volume was directly measured by serial tagged albumin concentration. Red blood cell volume was calculated using plasma volume and the peripheral blood hematocrit result. All volumes were presented as percentage deviation from ideal volumes. These ideal volumes were obtained using a patented formula incorporating ideal body weight as determined by Metropolitan Life tables. The peripheral blood hematocrit was compared with a "normalized" hematocrit, defined as the hematocrit value if plasma volume was adjusted to a normal whole blood volume.

CONCLUSIONS: Peripheral blood hematocrit may not accurately estimate red blood cell volume in a cohort of critically ill surgical patients. This remains to be validated in a larger group of patients, comparing these results with the double isotope technique.

RESULTS: Eighty-six data points were recorded for 40 patients with average age 61 ± 20 yr, APACHE II score 20 ± 6, and a 13% mortality rate. The primary reasons for admission were severe sepsis/septic shock (n = 11), hemorrhagic shock (n = 7), respiratory failure (n = 20), and cardiac failure (n = 2). Bland–Altman analysis showed a mean difference of 3.4 ± 7.8 hematocrit percentage points between normalized and peripheral blood hematocrit methods, with a 95% confidence interval of 1.7–5.1 and limits of agreement of ±15.2 hematocrit percentage points. Peripheral blood hematocrit was lower than the normalized hematocrit in 48% of measurements, higher in 17%, and equivalent in 35%.

 

 

對血管內皮生長因數在嚴重膿毒症及膿毒性休克中的研究

Vascular Endothelial Growth Factor in Severe Sepsis and Septic Shock

Sari Karlsson, Ville Pettilä, Jyrki Tenhunen, Vesa Lund, Seppo Hovilehto, Esko Ruokonen For the Finnsepsis Study Group

Department of Intensive Care Medicine, Tampere University Hospital, Finland. sari.karlsson@pshp.fi

Anesth Analg 2008 106: 1820-1826.

 

背景:已有研究顯示在嚴重膿毒症中,血管內皮生長因數(VEGF)的水準有所增高。我們通過對患有嚴重膿毒症的成年病人的VEGF水準的觀測,以研究其在預知發生臟器功能不全及院內死亡率中的作用。

方法:我們在芬蘭的24個多學科重症監護室(ICU)中設計了一個前瞻性的觀察性佇列研究,所有這些入住ICU的病人(共4500人)均為在2004.11.12005.2.28期間以嚴重膿毒症的標準進行過篩選,若他們符合嚴重膿毒症的診斷標準則予選擇入組。

結果:其中有470人符合嚴重膿毒症的診斷標準。在獲得知情同意後,我們留取了250位病人在入組當時(第0天)的實驗室血樣,以及215位病人在入組後72小時的血樣,再將這些血樣與30位健康個體的血樣比較。我們獲得在ICU內的死亡率為13.2%,院內死亡率為26%;並測得在0天時的血清VEGF的中值為423 pg/mL (其四分位數區間 [IQR] 159858 pg/mL),而在72h時的血清VEGF的中值為521 pg/mL (其四分位數區間 [IQR] 1821092pg/mL),而兩者均高於健康對照組(P值分別為0.0290.003)。低水準的血清VEGF濃度多與更嚴重的(持續臟器衰竭評分為3-4,高於0-2分者)腎衰及血液學功能障礙有關,且在死亡患者中其0天及72h時的血清VEGF濃度則明顯低於存活者(P值分別為0.01<0.01)。但通過受試者工作特性曲線分析顯示,在0天及72h的血清VEGF濃度的曲線下麵積分別為0.58 and 0.63(而其95%的可信區間分別為0.48-0.680.54-0.72, P值分別為0.10.009)。

結論:血清的VEGF濃度在嚴重膿毒症患者中有所增高,而低水準的血清VEGF濃度則多與血液學及腎功能障礙相關。我們雖可知死亡患者的血清VEGF濃度低於存活者,但將它作為嚴重膿毒症患者院內死亡率的預測依據尚不夠充分。

(劉沁譯 薛張綱校)

BACKGROUND: Vascular endothelial growth factor (VEGF) levels have been shown to be elevated in severe sepsis. We investigated the value of VEGF in predicting organ dysfunction and hospital mortality in adult patients with severe sepsis.

METHODS: We conducted a prospective observational cohort study in 24 closed multidisciplinary intensive care units (ICU) in Finland. All ICU admission episodes (4500) were screened for severe sepsis from November 1, 2004, to February 28, 2005. Patients were eligible if they fulfilled the criteria for severe sepsis.

RESULTS: Severe sepsis was found in 470 patients. Laboratory samples were obtained after informed consent from 250 patients at study entry (day 0) and from 215 patients after 72 h. These samples were compared with samples from 30 healthy individuals. The ICU mortality was 13.2% and hospital mortality 26%. Median serum VEGF concentrations on day 0 were 423 pg/mL (interquartile range [IQR] 159 and 858 pg/mL), and after 72 h were 521 pg/mL (IQR 182 and 1092 pg/mL), which were both higher than in healthy controls (P = 0.029 and 0.003, respectively). Low VEGF concentrations were associated with more severe renal and hematological dysfunction (Sequential Organ Failure Assessment scores 3-4 compared with scores 0-2). VEGF concentrations in day 0 and after 72 h were lower in nonsurvivors (P = 0.01 and <0.01, respectively) than in survivors, but the receiver operating characteristic curve analyses of concentrations of VEGF on day 0 and at 72 h revealed areas under the curve of 0.58 and 0.63 (95% confidence limits 0.48-0.68 and 0.54-0.72, P = 0.1 and 0.009, respectively).

CONCLUSIONS: VEGF concentrations are increased in patients with severe sepsis. Low concentrations are associated with hematological and renal dysfunction. VEGF concentrations were lower in nonsurvivors than in survivors, but did not adequately predict hospital mortality in patients with severe sepsis.

 

抗驚厥藥物的抗傷害性作用小鼠內臟疼痛模型

The Antinociceptive Effects of Anticonvulsants in a Mouse Visceral Pain Model

Radica M. Stepanovic-Petrovic, Maja A. Tomic, Sonja M. Vuckovic, Sonja Paranos, Nenad D. Ugresic, Milica S. Prostran, Slobodan Milovanovic, and Bogdan Boskovic

From the *Department of Pharmacology, Faculty of Pharmacy, {dagger}Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, and {ddagger}Military Medical Academy, Belgrade, Serbia

Anesth Analg 2008 106: 1897-1903.

 

背景:在多種神經病理性疼痛和炎性軀體疼痛模型中,有證據表明醯胺咪嗪、奧凱西平、加巴噴丁和托吡酯有抗傷害性刺激的作用。但這些資料都未表明此類藥物對內臟痛的潛在作用。該研究中,我們用扭體試驗作為小鼠內臟痛的模型研究和比較了醯胺咪嗪、奧凱西平、加巴噴丁和托吡酯的作用。除此以外,還檢驗了這些藥物對運動狀態的影響以比較用於治療急性內臟痛的耐受性。

方法:用乙酸扭體試驗評價抗驚厥藥物的抗傷害作用。用旋轉試驗測試其副作用。

結果:口服醯胺咪嗪(25–60 mg/kg 、奧凱西平(10–40 mg/kg )、加巴噴丁(10–70 mg/kg )和托吡酯(5–30 mg/kg )後,在扭體試驗中會使小鼠翻騰次數以劑量依賴的方式減少。在旋轉試驗中,醯胺咪嗪(60–140 mg/kg、奧凱西平(20–450 mg/kg)口服後會使小鼠旋轉時間以劑量和時間依從性方式明顯下降。使用最大劑量時,加巴噴丁(1000–2000 mg/kg和托吡酯(400–1500 mg/kg)不會明顯影響小鼠的運動功能。醯胺咪嗪、奧凱西平、加巴噴丁和托吡酯的治療指數(運動影響TD50/翻騰ED50)分別是>148.5>60.215.22.3

結論:這些結果提示,在小鼠扭體試驗模型中使用醯胺咪嗪、奧凱西平、加巴噴丁和托吡酯能有效地對抗傷害性刺激。在一定劑量範圍不會對運動產生影響。托吡酯是最有效和最易耐受的藥物。

(蔣宗明譯 薛張綱校)

BACKGROUND: There is evidence supporting the antinociceptive effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in various models of neuropathic pain as well as inflammatory somatic pain. Data are lacking on the antinociceptive potential of these drugs against visceral pain. In this study, we examined and compared the effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in the writhing test as a visceral pain model in the mouse. In addition, the influence of these anticonvulsants on motor performance was examined to compare the tolerability of these anticonvulsants when used against acute visceral pain.

METHODS: The antinociceptive effects of these anticonvulsants were examined in the acetic acid writhing test in mice. The side effect propensity of these drugs was examined using the rotarod test.

RESULTS: Carbamazepine (25–60 mg/kg; p.o.), oxcarbazepine (10–40 mg/kg; p.o.), gabapentin (10–70 mg/kg; p.o.), and topiramate (5–30 mg/kg; p.o.) caused a significant dose-dependent reduction the number of writhes in the writhing test. In the rotarod test, carbamazepine (60–140 mg/kg; p.o.) and oxcarbazepine (120–450 mg/kg; p.o.) significantly reduced the time spent on the rotarod in a dose- and time-dependent manner. Gabapentin (1000–2000 mg/kg; p.o.) and topiramate (400–1500 mg/kg; p.o.) did not produce significant impairment of motor performance at the highest doses used. The therapeutic index (motor impairing dose TD50/writhing ED50) values were topiramate (>148.5) > gabapentin (>60.2) > oxcarbazepine (15.2) > carbamazepine (2.3).

CONCLUSIONS: These results indicate that oxcarbazepine, gabapentin, and topiramate are effective in the writhing model in mice, in a dose range, which is not related to motor impairment; topiramate is the most potent and the most tolerable drug.

 

 

一項關於可樂定和膕窩神經組織阻滯後鎮痛持續時間的隨機、雙盲、安慰劑對照研究

Clonidine and Analgesic Duration After Popliteal Fossa Nerve Blockade: Randomized, Double-Blind, Placebo-Controlled Study

Jacques T. YaDeau, Vincent R. LaSala, Leonardo Paroli, Richard L. Kahn, Kethy M. Jules-Elysée, David S. Levine, Barbara L. Wukovits, and Jane Y. Lipnitsky

Department of Anesthesiology and Foot and Ankle Service, Department of Orthopedic Surgery at Hospital for Special Surgery, Weill Medical College of Cornell University, 535 E 70th St., New York, NY 10011.

Anesth Analg 2008 106: 1916-1920.

 

背景:測試將100 µg可樂定加入0.375%布比卡因 溶液中將延長膕窩神經組織的鎮痛時間的假說。

方法:選取99名入院擬行足部或踝部手術的術後患者進入隨機、雙盲、安慰劑對照研究佇列。使用30ml加入腎上腺素的0.375%布比卡因溶液為患者行膕窩神經阻滯。患者行膕窩神經阻滯時被隨機分為:不含可樂定的布比卡因組,100 µg 可樂定肌注組或含100µg可樂定的布比卡因組。患者同時採用腰硬聯合麻醉,隱神經阻滯,術後行病人自控靜脈鎮痛。評價指標為病人報告的鎮痛持續時間。

結果:可樂定阻滯組的鎮痛持續時間延長有統計學意義(含可樂定的布比卡因組為18 ± 6小時,可樂定肌注組為14 ± 7小時,對照組為15 ± 7小時,含可樂定的布比卡因組與對照組組間P = 0.016)。組間疼痛評分,鎮痛藥用量及鎮痛治療相關的副反應無差異。

結論:可樂定可明顯延長布比卡因膕窩神經阻滯的鎮痛持續時間。

(黃凝譯  薛張綱校)

 

BACKGROUND: We tested the hypothesis that 100 µg clonidine added to 0.375% bupivacaine would prolong the duration of analgesia from popliteal fossa nerve blockade.

METHODS: Ninety-nine patients scheduled for hospital admission after foot or ankle surgery entered this randomized, double-blind, placebo-controlled trial. Patients received a popliteal fossa block (nerve stimulator technique, via the posterior approach) using 30 mL 0.375% bupivacaine, with epinephrine. Patients were randomized to receive no clonidine, 100 µg clonidine IM, or 100 µg clonidine with bupivacaine for the popliteal block. Patients also received a combined spinal-epidural anesthetic, a saphenous nerve block, and postoperative IV patient-controlled analgesia. The primary outcome was patient-reported duration of analgesia.

RESULTS: Duration of analgesia was statistically longer in the block clonidine group (18 ± 6 h for clonidine with bupivacaine vs 14 ± 7 h for IM clonidine and 15 ± 7 h for control, P = 0.016 for control vs clonidine with bupivacaine). Pain scores, analgesic use, and side effects attributable to pain management were similar among groups.

CONCLUSIONS: Clonidine significantly prolongs the analgesic duration after popliteal fossa nerve blockade with bupivacaine.

 

低體溫和酸中毒對人全血的凝血有協同損害作用

Hypothermia and Acidosis Synergistically Impair Coagulation in Human Whole Blood

Daniel Dirkmann, MD, Alexander A. Hanke, MD, Klaus Görlinger, MD, and Jürgen Peters, MD

From the Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen, Universitätsklinikum Essen, Essen, Germany.

Anesth Analg 2008; 106:1627-1632

背景:各種不同的臨床設計報導了低體溫和酸中毒對凝血障礙的影響。我們評估了全血的凝血來確定低體溫和/或酸中毒對止血的作用。

方法:來自10名健康志願者(2女,8男)的全血樣本(3.000µL),加入40µL摩爾濃度增加的鹽酸酸化以達到血pH(α-pH固定計)介於7.07.37之間。用本質(InTEM TM)和非本質(ExTEM TM)活化測定法孵化30分鐘後,再用旋轉血栓彈性測定法分析凝血功能。為了評估溫度依賴性作用,所有試驗均在血液/血栓彈性測定儀的溫度30333639°C下分別進行。此外,通過添加細胞鬆弛素D進行了一項額外的非本質活化試驗,來檢測無血小板作用下的凝塊構成。

結果:正常pH下的低體溫導致了凝血時間延長[ExTEM: 65 s ± 3.6 (36°C)85 ± 4 (30°C), P < 0.001; 凝血時間, InTEM: 181 s ± 10 (36°C)226 ± 9, P < 0.001],凝塊形成時間延長[ExTEM: 105 s ± 5 (36°C)187 ± 6 (30°C), P < 0.001; InTEM: 101 s ± 5 (36°C)175 ± 7, P < 0.001],並且伴有α角的縮小,[ExTEM: 65.6 ± 1.8 (36°C)58 ± 1.1, P < 0.01; InTEM: 70.5 ± 1.8 (36°C)60.2 ± 1.5, P < 0.001]。最大凝塊硬度僅在InTEM測定法中顯著受損[56.9 mm ± 0.9 (36°C)52.7 ± 0.9, P < 0.05]。相反,正常體溫下酸中毒本身無明顯影響。酸中毒放大了低體溫的作用,並在本質和非本質活化測定中協同性損害凝血時間、α角並減小最大凝塊硬度。用細胞鬆弛素D消除血小板功能後進行的纖維蛋白凝塊形成試驗顯示沒有受損。在低體溫和/或酸中毒環境下凝塊溶解減少,而在高體溫下增加。

結論:在此次體外研究中,血栓彈性測定法顯示:酸中毒使低體溫引起的凝血改變惡化,而不伴低體溫的酸中毒對凝血無顯著影響。這種效應是由對凝血因數和血小板功能的抑制介導的。因此,37°C下進行的血栓彈性測定法高估了低體溫尤其伴酸中毒時凝血功能的完整性。

(唐李雋    馬皓琳  李士通 校)

BACKGROUND: Hypothermia and acidosis were reported to influence coagulopathy in different clinical settings. We evaluated whole blood coagulation to determine the effects of hypothermia and/or acidosis on hemostasis.

METHODS: Whole blood samples (3.000 µL) from 10 healthy volunteers (2 female, 8 male) were acidified by adding 40 µL of hydrochloric acid of increasing molarity to achieve a blood pH ({alpha}-stat) between 7.0 and 7.37, and coagulation was analyzed by rotational thromboelastometry after an incubation period of 30 min using both intrinsically (InTEM TM) and extrinsically (ExTEM TM) activated assays. To assess temperature-dependent effects, all tests were performed at blood/thromboelastometer temperatures of 30, 33, 36, and 39°C, respectively. An additional extrinsically activated test with addition of cytochalasin D was performed to examine clot formation without platelet contribution.

RESULTS: Hypothermia at a normal pH produced an increased coagulation time [ExTEM: 65 s ± 3.6 (36°C) vs 85 ± 4 (30°C), P < 0.001; coagulation time, InTEM: 181 s ± 10 (36°C) vs 226 ± 9, P < 0.001] and clot formation time [ExTEM: 105 s ± 5 (36°C) vs 187 ± 6 (30°C), P < 0.001]; clot formation time [InTEM: 101 s ± 5 (36°C) vs 175 ± 7, P < 0.001], as well as decreased {alpha}angle [ExTEM: 65.6 ± 1.8 (36°C) vs 58 ± 1.1, P < 0.01, P < 0.01; InTEM: 70.5 ± 1.8 (36°C) vs 60.2 ± 1.5, P < 0.001]. Maximum clot firmness was significantly impaired only in InTEM assays [56.9 mm ± 0.9 (36°C) vs 52.7 ± 0.9, P < 0.05]. In contrast, acidosis per se had no significant effects during normothermia. Acidosis amplified the effects of hypothermia, and synergistically impaired clotting times, {alpha}angle, and decreased maximum clot firmness, again in both extrinsically and intrinsically activated assays. Formation of a fibrin clot tested after abolition of platelet function by cytochalasin D was not impaired. Clot lysis decreased under hypothermic and/or acidotic conditions, but increased with hyperthermia.

CONCLUSIONS: In this in vitro study, hypothermia produced coagulation changes that were worsened by acidosis whereas acidosis without hypothermia has no significant effect on coagulation, as studied by thromboelastometry. This effect was mediated by the inhibition of coagulation factors and platelet function. Thus, thromboelastometry performed at 37°C overestimated integrity of coagulation during hypothermia in particular in combination with acidosis.




全身麻醉藥對腦結構發育和神經認知功能的影響

An Assessment of the Effects of General Anesthetics on Developing Brain Structure and Neurocognitive Function

Andreas W. Loepke, MD, PhD, FAAP*, and Sulpicio G. Soriano, MD, FAAP{dagger}

From the *Department of Anesthesia, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, and Institute of Pediatric Anesthesia, Cincinnati Children’s Hospital Research Foundation, Cincinnati, Ohio; and {dagger}Department of Anesthesia, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts.

Anesth Analg 2008; 106:1681-1707

背景:近來有研究發現全身麻醉藥可以導致一些非成熟動物模型的神經元細胞死亡。全世界每年有幾百萬的兒童在外科手術或放射檢查過程中用到揮發性麻醉藥,所以麻醉藥在新生兒或嬰兒誘發神經毒性的可能性在小兒麻醉的安全性方面引發了極大的關注。但是,將動物研究資料應用於臨床麻醉實踐仍存在不確定性。在本綜述中,我們評估了常用麻醉藥對人類和動物新生兒神經結構和神經認知功能影響的證據。

方法:在醫學資料庫,包括MedlineCinahlPubmed、美國麻醉醫師協會、國際麻醉研究協會、兒科麻醉協會和神經科學協會的年會摘要以及個人檔中查詢關於麻醉誘發神經毒性的資料。

結果:越來越多的研究發現多種麻醉藥可以使未成熟動物模型的神經結構發生變性。一些研究顯示動物在新生兒時期接受過麻醉,成年後有認知功能損害。目前還沒有前瞻性研究可以評估新生兒時期接受過麻醉後的兒童的神經認知功能。但是,一些回顧性綜述表明幼兒長時間麻醉後有暫時性的神經學後遺症,且較大的研究認明新生兒手術和麻醉後有長期的神經發育損害。

結論:動物模型中麻醉誘發神經變性的證據是令人注目的。雖然未在幼兒中前瞻性研究過這個現象,無對照的資料已經表明在生命早期接受過手術和麻醉後可能會有神經功能損害。倘若對公眾衛生有嚴重的含義,就必須在實驗室動物和幼兒中對這個現象進一步研究。

(張瑩譯  馬皓琳 李士通校)

BACKGROUND: Neuronal cell death after general anesthesia has recently been documented in several immature animal models. Worldwide, volatile anesthetics are used in millions of young children every year during surgical procedures and imaging studies. The possibility of anesthesia-induced neurotoxicity during an uneventful anesthetic in neonates or infants has led to serious questions about the safety of pediatric anesthesia. However, the applicability of animal data to clinical anesthesia practice remains uncertain. In the present review, we assess the evidence for the effects of commonly used anesthetics on neuronal structure and neurocognitive function in newborn humans and animals.

METHODS: Medical databases, including Medline, Cinahl, and Pubmed, abstract listings of the American Society of Anesthesiologists, International Anesthesia Research Society, Society for Pediatric Anesthesia, and Society for Neuroscience Annual Meetings, and personal files were queried regarding anesthesia-induced neurotoxicity.

RESULTS: A growing number of studies in immature animal models demonstrate degenerative effects of several anesthetics on neuronal structure. A few studies reveal cognitive impairment in adult animals after neonatal anesthesia. There are no prospective studies evaluating neurocognitive function in children after neonatal exposure to anesthetics. However, several retrospective reviews demonstrate temporary neurological sequelae after prolonged anesthetic exposure in young children and larger studies identify long-term neurodevelopmental impairment after neonatal surgery and anesthesia.

CONCLUSIONS: The evidence for anesthesia-induced neurodegeneration in animal models is compelling. Although this phenomenon has not been prospectively studied in young children, anecdotal data point toward the possibility for neurological impairment after surgery and anesthesia early in life. Given the serious implications for public health, further investigations of this phenomenon are imperative, both in laboratory animals and in young children.


右美托咪啶經鼻給藥與口服咪達唑侖在小兒麻醉術前用藥中的比較:一項雙盲隨機對照試驗

A Comparison of Intranasal Dexmedetomidine and Oral Midazolam for Premedication in Pediatric Anesthesia: A Double-Blinded Randomized Controlled Trial

Vivian M. Yuen, MBBS, FANZCA, FHKCA, FHKAM, Theresa W. Hui, MBBS, FANZCA, FHKCA, FHKAM, Michael G. Irwin, MBChB, MD, FRCA, FHKCA, FHKAM, and Man K. Yuen, MBBS, FANZCA, FHKCA, FHKAM

From the Department of Anesthesiology, Queen Mary Hospital, University of Hong Kong, Hong Kong.

Anesth Analg 2008; 106:1715-1721

背景:咪達唑侖在小兒術前用藥中最為常用。在麻醉誘導時它比父母在場或安慰劑在減輕焦慮、增加順從性方面更有效。已有研究提出{alpha}2 受體激動劑可樂定是一種替代藥品。右美托咪啶比可樂定有更強的{alpha}2 受體選擇性,且藥代動力學性質更有利。我們設計了這個前瞻性、隨機、雙盲、對照的試驗來評估右美托咪啶經鼻給藥在小兒術前用藥中應用是否和口服咪達唑侖一樣有效。

方法:96ASA I~II級擇期小手術的患兒隨機分為3組。M組術前口服咪達唑侖0.5 mg/kg(對乙醯氨基酚糖漿中)並經鼻給安慰劑。D0.5組和D1組分別經鼻給右美托咪啶0.5 1 µg/kg,以及對乙醯氨基酚糖漿。由一名研究者記錄患者鎮靜狀態、行為評分、血壓、心率以及氧飽和度直到麻醉誘導。還記錄恢復特徵。

結果:三組在父母分開可接受度、誘導時行為評分和蘇醒行為評分均無差異。D0.5組和D1組與M組相比,在與父母分開時更為鎮靜(P < 0.001)D1組的患者在麻醉誘導時明顯比M組鎮靜(P = 0.016)

結論:右美托咪啶經鼻給藥比口服咪達唑侖產生更多的鎮靜作用,但合作性相似並可接受。

(朱 慧譯 馬皓琳 李士通校)

BACKGROUND: Midazolam is the most commonly used premedication in children. It has been shown to be more effective than parental presence or placebo in reducing anxiety and improving compliance at induction of anesthesia. Clonidine, an {alpha}2 agonist, has been suggested as an alternative. Dexmedetomidine is a more {alpha}2 selective drug with more favorable pharmacokinetic properties than clonidine. We designed this prospective, randomized, double-blind, controlled trial to evaluate whether intranasal dexmedetomidine is as effective as oral midazolam for premedication in children.

METHODS: Ninety-six children of ASA physical status I or II scheduled for elective minor surgery were randomly assigned to one of three groups. Group M received midazolam 0.5 mg/kg in acetaminophen syrup and intranasal placebo. Group D0.5 and Group D1 received intranasal dexmedetomidine 0.5 or 1 µg/kg, respectively, and acetaminophen syrup. Patients’ sedation status, behavior scores, blood pressure, heart rate, and oxygen saturation were recorded by an observer until induction of anesthesia. Recovery characteristics were also recorded.

RESULTS: There were no significant differences in parental separation acceptance, behavior score at induction and wake-up behavior score. When compared with group M, patients in group D0.5 and D1 were significantly more sedated when they were separated from their parents (P < 0.001). Patients from group D1 were significantly more sedated at induction of anesthesia when compared with group M (P = 0.016).

CONCLUSIONS: Intranasal dexmedetomidine produces more sedation than oral midazolam, but with similar and acceptable cooperation.



補充供氧能否減少術後噁心嘔吐?隨機對照實驗的薈萃分析

Does Supplemental Oxygen Reduce Postoperative Nausea and Vomiting? A Meta-Analysis of Randomized Controlled Trials

Mukadder Orhan-Sungur, MD*{dagger}, Peter Kranke, MD, MBA, PhD{ddagger}, Daniel Sessler, MD§, and Christian C. Apfel, MD, PhD*||

From the *Outcomes Research Institute, and {dagger}Department of Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, Kentucky; {ddagger}Department of Anesthesiology, University of Wuerzburg, Wuerzburg, Germany; §Department of Outcomes Research, Cleveland Clinic Foundation; ||Perioperative Clinical Research Core, Department of Anesthesiology and Perioperative Care, University of California, San Francisco, California.

Anesth Analg 2008; 106:1733-1738

背景關於補充供氧降低術後噁心嘔吐(PONV)發生率的能力是不一致的,最初的研究表明它對減少PONV是有益處的,而隨後的試驗證明它不能減少PONV

方法:為了弄清補充供氧是否是減少PONV的一種有效和可靠的方法,我們對比較了圍手術期80%吸入氧濃度和 30%–40%吸入氧濃度影響PONV發生率的隨機對照試驗進行了系統回顧(MEDLINECochrane圖書館、手工查找和文獻目錄,無語言限制,到20063月為止)。對本次系統回顧而言,PONV被定義為術後24小時內的任何噁心、幹嘔和/或嘔吐。觀察的終點為早期PONV(0–6 h)、後期PONV (6–24 h)和總的PONV (0–24 h)。我們的薈萃分析包括了10個試驗的共1729名病人的資料:860名病人的吸入氧濃度為80%,另外869名病人的吸入氧濃度為30%–40%

結果:在吸入氧濃度為80%的病人中,發生早期、後期和總的PONV的相對危險度(95%可信區間)分別為0.91 [0.71–1.16]0.88 [0.69–1.11]0.91 [0.77–1.06]。對於早期、後期和總的噁心嘔吐的發生率的結果是相似的。

結論:最初的兩個研究表明給病人吸入濃度為80%的氧氣可以降低PONV的風險,但是這個陽性結果沒能被隨後的任何試驗證明。鑒於所有的可得到的證據,80%的吸入氧濃度不應該被再認為是減少總的PONV的一種有效或可靠的方法。

(吳進   馬皓琳 李士通 校)

BACKGROUND: Studies on the ability of supplemental oxygen to decrease the incidence of postoperative nausea and vomiting (PONV) are inconsistent, with initial studies suggesting benefit while subsequent trials demonstrate no decrease in PONV.

METHODS: To clarify whether supplemental oxygen is an effective and reliable method to reduce PONV, we performed a systematic review (MEDLINE, Cochrane Library, hand searching and bibliographies, with no language restriction, through March 2006) of randomized, controlled trials comparing perioperative 80% versus 30%–40% Fio2 on the incidence of PONV. For this systematic review, PONV was defined as any nausea, retching, and/or vomiting in the first 24 h after surgery. The end-points were early PONV (0–6 h), late PONV (6–24 h), and overall PONV (0–24 h). Data from 10 trials with 1729 patients were included in our meta-analysis: 860 received 80% Fio2 and 869 received 30%–40% Fio2.

RESULTS: In patients who received 80% Fio2,the relative risk (95% confidence intervals) of experiencing early PONV was 0.91 [0.71–1.16]; late PONV, 0.88 [0.69–1.11]; and overall PONV, 0.91 [0.77–1.06]. Results were similar for early, late, and overall nausea and vomiting.

CONCLUSIONS: The positive results of two initial studies reducing the risk for PONV in patients given 80% Fio2 were not confirmed by any of the subsequent trials. Considering all available evidence, 80% Fio2 should no longer be considered an effective or reliable method to reduce overall PONV.



芳香族麻醉藥對傷害性刺激引起的背角神經元反應的作用

The Effects of Aromatic Anesthetics on Dorsal Horn Neuronal Responses to Noxious Stimulation

Aubrey Yao, MD*, JongBun Kim, MD, PhD*{dagger}, Richard Atherley, BS*, Steven L. Jinks, PhD*, Earl Carstens, PhD{ddagger}, Sean Shargh, BS*, Alana Sulger, BS*, and Joseph F. Antognini, MD*{ddagger}

From the *Department of Anesthesiology and Pain Medicine, University of California, Davis, California; {dagger}Department of Anesthesia and Pain Medicine, Catholic University of Korea, Seoul, Korea; and {ddagger}Section of Neurobiology, Physiology and Behavior, University of California, Davis, California.

Anesth Analg 2008; 106:1759-1764

研究背景:氟化芳香族化合物的麻醉特性的原因可能是增強γ-氨基丁酸A型受體和/或抑制N-甲基-d-天冬氨酸(NMDA)受體。本研究假設抑制背角神經元對傷害性刺激的反應與苯酚(BNZ)、o-二氟聯苯和六氟苯(HFB)對NMDA受體作用的強度相關。

研究方法:大鼠在地氟醚麻醉下行T13-L1椎板切除術,細胞外記錄腰段脊髓神經元活性。停止給予地氟醚後確定每個芳香族麻醉藥的MAC。然後給予脊髓背角傷害性感受神經元在後爪的感受野一個長達5s的傷害性機械刺激並記錄0.8MAC1.2MAC時單個神經元的反應。同樣,對接受BNZHFB的去大腦大鼠在0–1.2 MAC時記錄這些反應。

研究結果:完整的大鼠中,BZNo-二氟聯苯和HFB在圍MAC範圍內濃度增加,其抑制背角神經元對傷害性刺激的反應與這些藥物離體阻斷NMDA受體的強度直接相關。去大腦大鼠中,1.2 MAC BNZ對傷害性感受反應的抑制達60%,且從0.8MAC1.2MAC神經元對傷害性刺激反應百分比進一步減少,近似於在整體大鼠中的發現。在去大腦大鼠中,HFB 引起劑量相關的MAC漸進性減少(最多減少25%),但是在整體大鼠中,MAC0.8增加至1.2使得神經元反應(非顯著性)增加。

結論:在整體大鼠中的發現提示氟化芳香族麻醉藥抑制背角神經元對傷害性刺激反應的作用機制與NMDA受體阻斷有關。上述結果結合在去大腦大鼠中的發現提示HFB的脊髓上效應(可能作用於γ

 

 
-氨基丁酸A型受體)可能對傷害性感受有易化作用。

(周雅春 李士通 馬皓琳 校)

BACKGROUND: Gamma-aminobutyric acid type A receptor potentiation and/or N-methyl-d-aspartate (NMDA) receptor inhibition might explain the anesthetic properties of fluorinated aromatic compounds. We hypothesized that depression of dorsal horn neuronal responses to noxious stimulation would correlate with the magnitude of effect of benzene (BNZ), o-difluorobenzene, and hexafluorobenzene (HFB) on NMDA receptors.

METHODS: Rats were anesthetized with desflurane. A T13-L1 laminectomy allowed extracellular recording of neuronal activity from the lumbar spinal cord. After discontinuing desflurane administration, MAC for each aromatic anesthetic was determined. A 5-s noxious mechanical stimulus was then applied to the hindpaw receptive field of nociceptive dorsal horn neurons, and single-neuron responses were recorded at 0.8 and 1.2 MAC. These responses were also recorded in decerebrate rats receiving BNZ and HFB at 0–1.2 MAC.

RESULTS: In intact rats, depression of responses of dorsal horn neurons to noxious stimulation by peri-MAC increases in BZN, o-difluorobenzene, and HFB correlated directly with their in vitro capacity to block NMDA receptors. In decerebrate rats, 1.2 MAC BNZ depressed nociceptive responses by 60%, with a further percentage decrease continuing from 0.8 to 1.2 MAC approximately equal to that found in intact rats. In decerebrate rats, HFB caused a progressive dose-related decrease in MAC (maximum 25%), but in intact rats, an increase from 0.8 to 1.2 neuronal response caused an (insignificant) increase in neuronal response.

CONCLUSIONS: The findings in intact rats suggest that NMDA blockade contributes to the depression of dorsal horn neurons to nociceptive stimulation by fluorinated aromatic anesthetics. These results, combined with the additional findings in decerebrate rats, suggest that supraspinal effects (perhaps on {gamma}-aminobutyric acid type A receptors) may have a supraspinal facilitatory effect on nociception for HFB.


局麻藥氨苯丁酯抑制PC12細胞中總的和L-型鋇電流

The Local Anesthetic Butamben Inhibits Total and L-Type Barium Currents in PC12 Cells

Laurentius J.A. Rampaart, MD, Jeroen P. Beekwilder, MSc, Gertrudis Th.H. van Kempen, BSc, Rutgeris J. van den Berg, PhD, and Dirk L. Ypey, PhD

From the Department of Neurophysiology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.

Anesth Analg 2008; 106:1778-1783

背景:氨苯丁酯或稱n-丁醯基-p-氨基苯甲酸酯是一種長效的實驗用局麻藥,硬膜外懸浮液注射用於治療慢性疼痛的治療。我們研究了Cav1.2/L-型鈣通道是否可能為氨苯丁酯的這種作用的一個靶位。

方法:用全細胞膜片鉗技術(電壓鉗)在未分化的大鼠PC12細胞上研究氨苯丁酯對這些通道的作用。Ba2離子被用作鈣通道電流中的載荷子,而使用不含K的溶液以排除K電流。

結果:500 µM的氨苯丁酯可逆性地抑制90% ± 3%(n = 15)的全細胞總鋇電流,而10 µM的硝苯吡啶抑制75% ± 7% (n = 6)的這種鋇電流。預暴露于氨苯丁酯繼而洗脫可將硝苯吡啶的抑制作用減至47% ± 5% (n = 10)。這些抑制作用與測量方法以及溶液中的藥物賦形劑(低於0.1%的乙醇;n = 6)無關。

結論:氨苯丁酯抑制PC12細胞中通過表達的鈣通道型的總鋇電流,包括Cav1.2/L-型通道。由於Cav1.2通道也可存在於人的傷害感受性C纖維,這一結果使得這些L-型通道可能與氨苯丁酯的鎮痛作用有關。

(黃施偉 譯,馬皓琳 李士通 校)

BACKGROUND: Butamben or n-butyl-p-aminobenzoate is a long-acting experimental local anesthetic for the treatment of chronic pain when given as an epidural suspension. We have investigated whether Cav1.2/L-type calcium channels may be a target of this butamben action.

METHODS: The effect of butamben on these channels was studied in undifferentiated rat PC12-cells with the whole-cell patch-clamp technique in voltage-clamp. Ba2+ ions were used as the charge carriers in the calcium channel currents, whereas K+ currents were removed using K+ free solutions.

RESULTS: Butamben 500 µM reversibly suppressed the total whole-cell barium current by 90% ± 3% (n = 15), whereas 10 µM nifedipine suppressed this barium current by 75% ± 7% (n = 6). Preexposure to butamben followed by washout decreased the inhibition by nifidepine to 47% ± 5% (n = 10). These suppressive effects were not due to the measurement procedure and the drug vehicles in the solutions (<0.1% ethanol; n = 6).

CONCLUSIONS: Butamben inhibits the total barium current through expressed calcium channel types in PC12 cells, including Cav1.2/L-type channels. Because Cav1.2 channels may also occur in human nociceptive C fibers, this result allows the possibility that these L-type channels are involved in the analgesic action of butamben.




游離皮質醇在敗血症及感染性休克中的應用

Free Cortisol in Sepsis and Septic Shock

Stepani Bendel, MD*, Sari Karlsson, MD{dagger}, Ville Pettilä, MD, PhD{ddagger}, Pekka Loisa, MD§, Marjut Varpula, MD{ddagger}, Esko Ruokonen, MD, PhD* For the Finnsepsis Study Group

From the Department of Intensive Care, *Kuopio University Hospital, Kuopio, Finland, {dagger}Tampere University Hospital, Tampere, Finland, {ddagger}Helsinki University Hospital, Helsinki, Finland, and §Päijät-Häme Central Hospital, Lahti, Finland.

Anesth Analg 2008; 106:1813-1819

背景:嚴重敗血症可以通過啟動下丘腦垂體軸來增加皮質醇的產生。在一些研究中,基於促腎上腺皮質激素刺激試驗或皮質醇基礎測量值來開展的氫化考的松替代治療已改善了結果。因為只有皮質醇的游離部分是有活性的,在危重病人中測定游離皮質醇可能比監測總皮質醇更有意義。我們測定了嚴重敗血症患者的總皮質醇及游離皮質醇並將其濃度與預後作了相關分析。

方法:在一項前瞻性研究中,嚴重敗血症患者的定義按照美國胸外科醫師學會/危重病醫學會的標準。研究開始後的24小時內抽取血樣。使用電化學發光免疫分析法測定血清皮質醇。並使用Coolens法計算血清游離皮質醇的濃度。

結果:收集125位患者的血樣,其中62位為嚴重敗血症,63位為感染性休克。醫院死亡率為21%。血清游離皮質醇計算值與血清總皮質醇濃度有很好的相關性(r = 0.90, P < 0.001)。敗血症及感染性休克的患者總皮質醇濃度無差別(728 ± 386 nmol/L793 ± 439 nmol/L, P = 0.44)。死亡組血清游離皮質醇的計算值(209 ± 151 nmol/L)與血清總皮質醇濃度(980 ± 458 nmol/L),與存活組(119 ± 111 nmol/L 704 ± 383 nmol/L相比更高( P = 0.002)。根據定義,腎上腺功能不全的發生率從8%54%不等。

結論:臨床上,對於接受皮質醇治療的嚴重感染及感染性休克病人,游離皮質醇的計算值不能為鑒別病人提供基本資訊。

(裘毅敏   馬皓琳 李士通 校)

BACKGROUND: Severe sepsis activates the hypothalamopituitary axis, increasing cortisol production. In some studies, hydrocortisone substitution based on an adrenocorticotropic hormone-stimulation test or baseline cortisol measurement has improved outcome. Because only the free fraction of cortisol is active, measurement of free cortisol may be more important than total cortisol in critically ill patients. We measured total and free cortisol in patients with severe sepsis and related the concentrations to outcome.

METHODS: In a prospective study, severe sepsis was defined according the American College of Chest Physicians/Society of Critical Care Medicine criteria. Blood samples were drawn within 24 h of study entry. Serum cortisol was analyzed by electrochemiluminescence immunoassay. The Coolens method was used for calculating serum free cortisol concentrations.

RESULTS: Blood samples were collected from 125 patients, of whom 62 had severe sepsis and 63 septic shock. Hospital mortality was 21%. Calculated free serum cortisol correlated well with serum total cortisol (r = 0.90, P < 0.001). There was no difference in the total cortisol concentrations in patients with sepsis and septic shock (728 ± 386 nmol/L vs 793 ± 439 nmol/L, P = 0.44). Nonsurvivors had higher calculated serum free (209 ± 151 nmol/L) and total (980 ± 458 nmol/L) cortisol concentrations than survivors (119 ± 111 nmol/L, P = 0.002, and 704 ± 383 nmol/L, P = 0.002). Depending on the definition, the incidence of adrenal insufficiency varied from 8% to 54%.

CONCLUSIONS: Clinically, calculation of free cortisol does not provide essential information for identification of patients who would benefit from corticoid treatment in severe sepsis and septic shock.

 

 

 

複雜區域疼痛綜合征I型中血漿5羥色胺濃度升高

Increased Plasma Serotonin in Complex Regional Pain Syndrome Type 1

Feikje Wesseldijk, MD*, Durk Fekkes, PhD{dagger}, Frank J. Huygen, MD, PhD*, Elly Bogaerts-Taal, BSc{dagger}, and Freek J. Zijlstra, PhD*

From the Departments of *Anesthesiology and {dagger}Neuroscience and Psychiatry, Erasmus MC, Rotterdam, The Netherlands.

Anesth Analg 2008; 106:1862-1867

背景:複雜區域疼痛綜合征I(CRPS1)病人通過應用5-羥色胺2A受體拮抗劑酮色林能達到一些改善。我們測定CRPS1過程中5-羥色胺的血漿水準,比較這些水準與疾病特徵的相關性。

方法:選擇35例患CRPS13年的病人和35例年齡一致的健康對照,測定血漿5-羥色胺。

結果:血漿5-羥色胺水準分別是411 ± 263 nmol/L 29 ± 18 nmol/L (P < 0.001) 與疾病特性沒有相關性。

結論CRPS1病人的血漿5-羥色胺水準明顯升高提示在這一疾病的過程中5-羥色胺起著重要作用。然而,因為與獨特的疾病特徵缺乏相關性,5-羥色胺可能只是CRPS1的一系列介導劑中的一員。

(彭中美 馬皓琳 李士通 校)

BACKGROUND: In patients with complex regional pain syndrome type 1 (CRPS1), some improvement can be achieved by the administration of ketanserin, a 5-HT2A receptor antagonist. We measured plasma levels of serotonin (5-HT) during CRPS1 and correlated these levels with disease characteristics.

METHODS: Plasma 5-HT was measured in 35 patients who had CRPS1 for 3 yr and compared with 35 age-matched healthy controls.

RESULTS: The plasma 5-HT levels were 411 ± 263 nmol/L and 29 ± 18 nmol/L, respectively (P < 0.001). No correlations with disease characteristics were observed.

CONCLUSIONS: The markedly elevated levels of plasma 5-HT in CRPS1 patients suggest a role for 5-HT during the course of this disease. However, because of the lack of correlations with distinct disease characteristics, 5-HT is probably one of a number of mediators in CRPS1.


大鼠內嗎啡肽的脊柱鎮痛效應:行為和G蛋白功能研究

The Spinal Antinociceptive Effects of Endomorphins in Rats: Behavioral and G Protein Functional Studies

Hong Xie, MD, PhD*{dagger}, James H. Woods, PhD*, John R. Traynor, PhD*, and Mei-Chuan Ko, PhD*{ddagger}

From the *Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan; {dagger}Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin, China; and {ddagger}Department of Psychology and Graduate Institute of Life Science, National Cheng Chi University, Taipei, Taiwan.

Anesth Analg 2008; 106:1873-1881

背景:內嗎啡肽-1和內嗎啡肽-2µ型阿片類受體的高度選擇性內源肽。但是,它們功能的效能和選擇性還是有爭論的。在此研究中,我們將鞘內給內嗎啡肽-1和內嗎啡肽-2對傷害感受分析及G蛋白活化的影響作用與一個高度有效的µ-阿片受體激動劑[d-Ala2,N-Me-Phe4,Gly5-ol]-腦啡肽(DAMGO)的這些作用作了系統性比較。

方法:用雄性斯普拉-道來大鼠製造急性和炎性疼痛模型,來比較抗痛效應的持續時間和強度。用激動劑-受激[35S]GTPγS結合來觀察脊髓和丘腦膜中受體-G蛋白水準的機能活動。另外,用每個受體類型的選擇性拮抗劑來驗證大鼠脊髓中內嗎啡肽的功能選擇性。

結果:在急性疼痛模型中,鞘內注射後,內嗎啡肽-1和內嗎啡肽-2DAMGO產生較少的抗痛效應。DAMGO、內嗎啡肽-1和內嗎啡肽-2刺激的[35S]GTPγS結合的濃度-反應曲線顯示,內嗎啡肽-1和內嗎啡肽-2DAMGO在脊髓和丘腦膜,產生較少的G蛋白啟動 (即約50%–60%)。此外,鞘內注射內嗎啡肽引起的抗痛作用被µ-阿片受體選擇性拮抗劑納曲酮阻滯(P < 0.05),但不會被δκ-阿片受體拮抗劑naltrindole nor-binaltorphimine所阻滯 (P > 0.05)

結論:內嗎啡肽是G蛋白在脊髓和丘腦µ阿片受體活化的部分激動劑。體內和體外的測量結果都顯示DAMGO比內嗎啡肽更有效。脊髓內嗎啡肽的抗痛效應可能在53%84%範圍內,這依賴於傷害刺激的強度和模式。

(張曦 譯,馬皓琳 李士通 校)

BACKGROUND: Endomorphin-1 and endomorphin-2 are endogenous peptides that are highly selective for µ-opioid receptors. However, studies of their functional efficacy and selectivity are controversial. In this study, we systematically compared the effects of intrathecal (i.t.) administration of endomorphin-1 and -2 on nociception assays and G protein activation with those of [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), a highly effective peptidic µ-opioid receptor agonist.

METHODS: Male Sprague-Dawley rats were used. Acute and inflammatory pain models were used to compare the duration and magnitude of antinociception. Agonist-stimulated [35S]GTP{gamma}S binding was used to observe the functional activity at the level of the receptor-G protein in both spinal cord and thalamic membranes. In addition, antagonists selective for each receptor type were used to verify the functional selectivity of endomorphins in the rat spinal cord.

RESULTS: After i.t. administration, endomorphin-1 and -2 produced less antinociceptive effects than DAMGO in the model of acute pain. Concentration–response curves for DAMGO-, endomorphin-1-, and endomorphin-2-stimulated [35S]GTP{gamma}S binding revealed that both endomorphin-1 and -2 produced less G protein activation (i.e., approximately 50%–60%) than DAMGO did in the membranes of spinal cord and thalamus. In addition, i.t. endomorphin-induced antinociception was blocked by µ-opioid receptor selective dose of naltrexone (P < 0.05), but not by {delta}- and {kappa}-opioid receptor antagonists, naltrindole and nor-binaltorphimine (P > 0.05).

CONCLUSIONS: Endomorphins are partial agonists for G protein activation at spinal and thalamic µ-opioid receptors. Both in vivo and in vitro measurements together suggest that DAMGO is more effective than endomorphins. Spinal endomorphins’ antinociceptive efficacy may range between 53% and 84% depending on the intensity and modality of the nociceptive stimulus.


鎮痛藥物曲馬多可以起到辣椒素暫態電位受體—1激動劑的作用

The Analgesic Drug, Tramadol, Acts as an Agonist of the Transient Receptor Potential Vanilloid-1

Rita Marincsák, MD*, Balázs I. Tóth, MSc*{dagger}, Gabriella Czifra, PhD*, Tamás Szabó, MD, PhD{ddagger}, László Kovács, MD, PhD*{dagger}, and Tamás Bíró, MD, PhD*{dagger}

From the *Department of Physiology, {dagger}Cell Physiology Research Group of the Hungarian Academy of Sciences, and {ddagger}Department of Pediatrics, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Debrecen, Hungary.

Anesth Analg 2008; 106:1890-1896

背景:曲馬多作為一種有效的鎮痛藥物被廣泛應用於臨床治療。曲馬多的作用機制主要表現在對µ型阿片類受體的激動作用,抑制神經遞質再攝取,抑制傷害性疼痛系統的各種電壓和配體門控離子通道。因為已有研究顯示辣椒素暫態電位受體—1(TRPV1, "辣椒素受體")可以起到痛覺中樞積分分子的作用,所以本次研究的目的是為了證實TRPV1在曲馬多的複合作用機制中起的作用。

方法:為了達到實驗目的,我們使用單細胞Ca成像技術和螢光成像平板分析測定中國倉鼠卵巢(CHO)細胞異源性過度表達TRPV1

結果:我們發現以下結果:(1)曲馬多和辣椒素這個熟知的辣椒素受體激動劑一樣,呈濃度依賴性地顯著增加CHO細胞TRPV1內流鈣離子;(2)該作用可以被TRPV1拮抗劑capsazepine 可逆性地阻止;(3)重複給予曲馬多會造成顯著的快速耐藥性;(4)曲馬多不修飾鈣對照(無傳病媒介表達)CHO細胞中的內流鈣離子。

結論:總之,這些發現都強烈支持這一新奇而有趣的觀念:曲馬多可以起到TRPV1激動劑的作用。考慮到跟隨著TRPV1對感覺神經元的激動作用之後的是血管神經肽的局部釋放和傳入神經纖維的顯著脫敏作用(因此終止痛覺),我們的發現在解釋曲馬多的鎮痛作用的同時也可以說明曲馬多常見但“意外的”局部副作用(如引發灼痛和紅斑)。

(薑旭暉 馬皓琳 李士通 校)

BACKGROUND: Tramadol is an effective analgesic substance widely used in medical practice. Its therapeutic action have been mainly attributed to the activation of µ-opioid receptors as well as to the inhibition of neurotransmitter reuptake mechanisms and various voltage- and ligand-gated ion channels of the nociceptive system. As transient receptor potential vanilloid-1 (TRPV1, "the capsaicin receptor") has been shown to function as a central integrator molecule of pain sensation, our aim in the current study was to define the involvement of TRPV1 in the complex mechanism of action of tramadol.

METHODS: To achieve these goals, we used single-cell Ca-imaging as well as fluorescent image plate reader assays on Chinese hamster ovary (CHO) cells heterologously over-expressing TRPV1.

RESULTS: We found that (1) tramadol, similar to the well-known TRPV1 agonist, capsaicin, significantly increased [Ca2+]i of TRPV1-CHO cells in a concentration-dependent fashion; (2) its effect was reversibly prevented by the TRPV1 antagonist capsazepine; (3) repeated application of tramadol resulted in marked tachyphylaxis; and (4) tramadol did not modify [Ca2+]i in control (empty vector expressing) CHO cells.

CONCLUSIONS: Collectively, these findings strongly support the intriguing and novel concept that tramadol acts as an agonist of TRPV1. Considering that activation of TRPV1 on sensory neurons is followed by a local release of vasoactive neuropeptides and a marked desensitization of the afferent fibers (hence termination of pain sensation), our findings may equally explain both the desired analgesic as well as the often-seen, yet "unexpected," local side effects (e.g., initiation of burning pain and erythema) of tramadol.


電神經刺激或超聲引導側位矢狀面的鎖骨下阻滯:隨機、對照、觀察者單盲的比較性研究

Electrical Nerve Stimulation or Ultrasound Guidance for Lateral Sagittal Infraclavicular Blocks: A Randomized, Controlled, Observer-Blinded, Comparative Study

Axel R. Sauter, MD*, Michael S. Dodgson, FRCA{dagger}, Audun Stubhaug, DMSc{dagger}, Anne Marie Halstensen, CRNA{dagger}, and Øivind Klaastad, DMSc{dagger}

*Faculty of Medicine, University of Oslo and {dagger}Division of Anaesthesiology and Intensive Care Medicine, Rikshospitalet University Hospital, Oslo, Norway.

Anesth Analg 2008; 106:1910-1915

背景:超聲引導經常用於鎖骨下臂叢神經阻滯。這次研究中,我們比較電神經刺激和超聲引導用於側位矢狀面的鎖骨下阻滯。

方法80名患者,ASA1-2級,隨機分成神經刺激組(NS組)和超聲引導組(US組)。兩組中的臂叢神經阻滯藥物為0.6mL/kg甲呱卡因(15 mg/mL),含腎上腺素(2.5 µg/mL)。對於超聲引導阻滯,局麻藥從顱後注射到腋動脈。一位元觀察者在不知道阻滯方法的情況下評估阻滯並詢問患者。阻滯成功的定義為肘部遠端的所有五根神經出現無痛或者麻痹。主要的結果變數為麻醉到可以手術的時間、阻滯過程中量化的不適程度及止血帶壓迫缺血相關的疼痛數位評定量表(1-10)

結果NS組和US組的阻滯操作時間分別是4.3分鐘 (標準差1.3)4.1分鐘 (標準差1.3) (P = 0.64)。感覺阻滯的起效時間分別為13.7分鐘 (標準差6.6)13.9分鐘 (標準差5.8) (P = 0.99)。兩組到可以手術的時間均為18.1分鐘 (標準差分別為6.66.0) (P = 0.99)。與阻滯過程相關的不適度的中位數兩組都是1 (P = 0.92),止血帶疼痛的中位數NS0.5US1(P =0.32)。成功率NS85%US95%,兩組之間沒有顯著性差異(P = 0.26)

結論:我們得出的結論是無論是用神經刺激還是超聲引導來進行側位矢狀面的鎖骨下阻滯都能取得良好的結果。使用超聲引導使局麻藥從顱後注射到腋動脈顯得更有可行性。

(唐亮   馬皓琳 李士通 校)

BACKGROUND: Ultrasound guidance is frequently used to perform infraclavicular brachial plexus blocks. In this study, we compared electrical nerve stimulation and ultrasound guidance for the lateral sagittal infraclavicular block.

METHODS: Eighty patients, ASA 1–2, were randomized for either nerve stimulation (group NS) or ultrasound-guided blocks (group US). The brachial plexus was anesthetized with 0.6 mL/kg mepivacaine (15 mg/mL) with epinephrine (2.5 µg/mL) in both groups. For ultrasound-guided blocks, local anesthetic was injected cranioposterior to the axillary artery. An observer who was blinded for the method assessed the blocks and questioned the patients. Successful block was defined as analgesia or anesthesia of all five nerves distal to the elbow. The main outcome variables were the time until readiness for surgery, quantified discomfort during the block, and pain related to tourniquet ischemia on a numeric rating scale (0–10).

RESULTS: Block performance time was 4.3 min (sd 1.3) and 4.1 min (sd 1.3) (P = 0.64) in group NS and group US, respectively. Onset time for sensory block was 13.7 min (sd 6.6) and 13.9 min (sd 5.8), (P = 0.99). The time until readiness for surgery was 18.1 min in both groups (sd 6.6 and 6.0) (P = 0.99). Median discomfort related to the block procedure was 1 in both groups (P = 0.92), and median tourniquet pain was 0.5 in group NS and 1 in group US (P = 32). Differences in success rates, between 85% in group NS and 95% in group US, were not significant (P = 0.26).

CONCLUSIONS: We conclude that favorable results can be obtained when either nerve stimulation or ultrasound guidance is used for lateral sagittal infraclavicular block. Using ultrasound, local anesthetic injection cranioposterior to the artery appears feasible.