Table of Contents

June 2008

 

CARDIOVASCULAR ANESTHESIOLOGY:

经皮吹入氧气并不能改善心脏手术病人胸骨伤口的氧合

章一静译,薛张纲校

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.

低体温和酸中毒对人全血的凝血有协同损害作用

唐李隽    马皓琳  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:

评估麻醉药物作用的策略和实验模型:对神经系统发育的影响

陶颖莹 陈杰

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.

对新生儿大脑的神经保护对策

宣丽真译 薛张纲校

Neuroprotective Strategies for the Neonatal Brain (Review Article)

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

Anesth Analg 2008 106: 1670-1680.

全身麻醉药对脑结构发育和神经认知功能的影响

张莹译  马皓琳 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.

全身麻醉诱导新生小鼠脊髓凋亡性神经退行性变

於章杰 陈杰

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.

小计量异丙酚引起乳鼠大脑神经元凋亡

夏俊明译 薛张纲校

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.

右美托咪啶经鼻给药与口服咪达唑仑在小儿麻醉术前用药中的比较:一项双盲随机对照试验

慧译 马皓琳 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:

喉显微外科手术期间七氟烷吸入麻醉和丙泊酚/瑞芬太尼静脉麻醉对唾液分泌的影响:一项前瞻性、随机、对照研究

杜唯佳 陈杰

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.

术前口服Passiflora减轻门诊病人的焦虑:一项双盲,安慰剂控制的研究

孙鹏飞译 薛张纲校

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.

补充供氧能否减少术后恶心呕吐?随机对照实验的荟萃分析

吴进   马皓琳 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:

腹腔镜下减肥手术期间输注右旋美托咪啶:对复苏的影响

张燕 陈杰

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.

在人低剂量吸入七氟醚后可以减少粒细胞-血小板的聚集作用

施颖译,薛张纲校

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.

芳香族麻醉药对伤害性刺激引起的背角神经元反应的作用

周雅春 李士通 马皓琳

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激酶抑制剂可增强丙泊酚对大鼠支气管平滑肌收缩的抑制作用

潘钱玲 陈杰

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.

延长使用异氟醚、丙泊酚、右旋美托咪定、氯胺酮对于成年鼠神经细胞增殖的影响

秦敏菊译 薛张纲校

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.

局麻药氨苯丁酯抑制PC12细胞中总的和L-型钡电流

黄施伟 译,马皓琳 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:

评判手术病人外周血细胞比容的应用:不能很好反映真实血细胞容量

刘婷洁译,薛张刚校

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:

游离皮质醇在败血症及感染性休克中的应用

裘毅敏   马皓琳 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.

对血管内皮生长因子在严重脓毒症及脓毒性休克中的研究

刘沁译 薛张纲校

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-氧化亚氮的全身麻醉下剖腹产手术中时BIS值的研究:初产妇和经产妇的比较。

王腾 陈杰

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:

腹部大手术术后给予氯胺酮可降低吗啡用量:一项前瞻性、随机、双盲、对照研究

陈伟 陈杰

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.

复杂区域疼痛综合征I型中血浆5羟色胺浓度升高

彭中美 马皓琳 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.

围术期使用加巴喷丁对整形外科病人鞘内注射吗啡引起的术后瘙痒症的保护作用

王鹏 陈杰

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.

大鼠内吗啡肽的脊柱镇痛效应:行为和G蛋白功能研究

张曦 译,马皓琳 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受体的表达及对NMDA受体离子流的调节作用

赵燕星 陈杰

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.

镇痛药物曲马多可以起到辣椒素瞬时电位受体—1激动剂的作用

姜旭晖 马皓琳 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.

抗惊厥药物的抗伤害性作用小鼠内脏疼痛模型

蒋宗明译 薛张纲校

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.

伏核内多巴胺D2样受体与氧化亚氮(N2O)的镇痛作用

张江玲 陈杰

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.

电神经刺激或超声引导侧位矢状面的锁骨下阻滞:随机、对照、观察者单盲的比较性研究

唐亮   马皓琳 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.

一项关于可乐定和腘窝神经组织阻滞后镇痛持续时间的随机、双盲、安慰剂对照研究

黄凝译  薛张纲校

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.

 

评估麻醉药物作用的策略和实验模型:对神经系统发育的影响

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.

 

儿科及产科手术的发展使人们对麻醉持续时间及复杂性要求提高。有报道称麻醉药物能对发育中鼠大脑产生广泛、剂量相关性的细胞凋亡。由于其他灵长类动物有着与人类相似的生理、药理、代谢及繁殖系统,妊娠阶段尤为显著,所以猴一向被视为非常优良的评估麻醉药物潜在神经毒性的动物模型。大脑对儿科麻醉药物的神经作用的易感期受快速突触发生过程(又称大脑生长过程)的影响。为了将麻醉药物对儿童可能的危害作用降至最低,麻醉操作中需考虑以下问题:

1.儿科麻醉中常用麻醉药物(吸入麻醉药、咪唑安定、氯胺酮及笑气)与大脑细胞损伤间存在怎样的相关性

2.是否要考虑类效应还是分别分析每种药物的影响作用

3.是否存在麻醉药物相互影响从而产生大脑细胞损伤

4.人类发育的哪一阶段更易受麻醉药物影响。

遗传药理/系统生物学方法对加深大脑相关性生物过程(包括神经元可塑性、神经毒性作用)的理解极为有用。由于神经毒性作用的表达存在复杂性及暂时性因素,所以遗传药理/系统生物学方法可以加强我们对麻醉药诱导的生物过程的理解。而本综述的主要目的是阐述使用这些方法、模型及相关保护措施尤其考虑到麻醉药物诱导发育中神经细胞死亡这一问题。

本文之后许多讨论基于的实验都采用氯胺酮为主。这主要是由于早期的实验以氯胺酮为主,且大量临床前试验如对于啮齿类动物及灵长类动物的麻醉药物实验也采用氯胺酮。尽管在儿科麻醉操作中氯胺酮使用相对有限,但相关研究的发现有力的证实其作用与n-甲基-d-天门冬氨酸拮抗剂相似。本文中作者对氯胺酮的着重讲述并不意味氯胺酮比其他麻醉药引起的神经退行性变可能性大,这只是由于我们已掌握的大量氯胺酮效应的基础数据。

(陶颖莹 陈杰 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.

 

全身麻醉诱导新生小鼠脊髓凋亡性神经退行性变

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:麻醉药物可触发新生鼠大脑的凋亡性神经退行性变;然而这种神经退行性变是否会发生于脊髓--这一麻醉镇痛药物的重要靶点,仍然未知。

方法:7日龄鼠随机暴露于空气或75%笑气-0.75%异氟醚-氧气的混合气体6小时(每组n19)。在气体暴露结束时检测腰部脊髓的细胞凋亡Caspase-3的含量(每组n3)。使用甩尾痛觉测试仪在出生后第8、第15、第三30天评价伤害反应的发育情况(每组n3)。在出生后第30d使用旋转实验评价运动反应。

结果:笑气-异氟醚增加脊髓中的含细胞凋亡蛋白酶caspase-3神经元的数量(P < 0.01)。尽管损伤较多发生于脊髓腹侧角,运动损伤并未发生(P > 0.05)。在测试的三个发育阶段并没观察到小鼠对伤害的功能效应(P > 0.05)。

结论:麻醉药物诱导新生鼠脊髓神经的凋亡;然而,这种损伤是否引起功能异常是未明的。麻醉药物的使用并不影响运动或对伤害刺激的反应。需要进一步研究局麻技术是否有引起脊髓神经凋亡的潜在危害。

(於章杰 陈杰 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.

 

喉显微外科手术期间七氟烷吸入麻醉和丙泊酚/瑞芬太尼静脉麻醉对唾液分泌的影响:一项前瞻性、随机、对照研究

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:提供清晰的手术视野是喉显微外科手术麻醉要求之一,因此期望麻醉药产生较少的唾液分泌。七氟烷吸入麻醉和丙泊酚/瑞芬太尼全凭静脉麻醉在喉显微外科手术中被广泛应用,然而,有关七氟醚和丙泊酚/瑞芬太尼各自对于唾液分泌影响的比较研究很少。

方法40名行喉显微外科手术的患者随机实施七氟醚或丙泊酚/瑞芬太尼麻醉。比较两实验组的唾液流速,唾液成分,手术操作前为了看清喉部解剖分层而进行的吸引次数,以及术后残余分泌物总量。

结果:丙泊酚/瑞芬太尼组实验者的平均唾液分泌速度较七氟烷组明显增高(0.53 ± 0.39 vs 0.28 ± 0.15 mL/min, P < 0.001)。手术操作前为了喉部分清晰而进行的吸引次数,在丙泊酚/瑞芬太尼组中也是明显增多(5.0 ± 2.3 vs 2.1 ± 1.5, P < 0.001)。丙泊酚/瑞芬太尼组实验者术后口腔和口咽部的平均残余分泌物总量也增多(2.13 ± 0.59 vs 0.45 ± 0.32 mL, P < 0.001)。此外,两组收集的分泌物中还观察到了氯离子浓度水平有明显的差异(七氟烷组; 93 ± 19 vs 丙泊酚/瑞芬太尼组; 135 ± 58 U/L, P = 0.004)

结论:在喉部手术期间,丙泊酚/瑞芬太尼静脉麻醉比七氟醚吸入麻醉的唾液分泌更加活跃。

(杜唯佳 陈杰 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.

 

腹腔镜下减肥手术期间输注右旋美托咪啶:对复苏的影响

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,一种受体激动剂,有显著的麻醉和镇痛效应。作者设计这项前瞻性,随机,双盲,安慰剂对照研究,以评估在腹腔镜下减肥手术后,右旋美托咪啶对术后早期和晚期复苏质量的影响。

法: 80ASA II–III级病态肥胖性患者,随机分为四组: 对照组输注生理盐水;右旋美托咪啶0.2组接受右旋美托咪啶0.2 µg · kg–1 · h–1;右旋美托咪啶0.4组接受右旋美托咪啶0.4 µg · kg–1 · h–1;右旋美托咪啶0.8组接受右旋美托咪啶0.8 µg · kg–1 · h–1。平均动脉压维持在诱导前基础值的±25 %。记录围手术期血流动力学,术后疼痛评分,复苏期间应用镇痛药和止吐药量等。评估术后1d2d7d疼痛程度,镇痛药的需求量,病人对疼痛处理的满意度,康复质量,及饮食摄入的恢复和肠功能的恢复。

果:右旋美托咪啶0.20.40.8组地氟醚吸入浓度分别减少了19%,20%,和22%。但未能加快麻醉显效。虽然四组中术中血流动力学相似,但麻醉后恢复室(PACU)右旋美托咪啶0.2 0.40.8组较对照组动脉血压较低 P<0.05)。在右美托咪啶组PACU的停留时间明显缩短(右美托咪啶组81 ± 31 87 ± 24min 对照组为104 ± 33 min, P < 0.05)。在PACU中芬太尼用量,右旋美托咪啶 0.20.40.8组比对照组显著减少(分别为113 ± 85, 108 ± 67, and 120 ± 78 vs 187 ± 99 µg, P < 0.05) 。右旋美托咪啶组需要止吐治疗患者分别为 30%30%10% ,对照组为70%。但四个组中,术后1天和2天病人自控镇痛吗啡的需求量并没有不同。在PACU,术后1天,2天和7天,疼痛评分组间无显著差异。四组中,后期评分,肠道功能的恢复和出院时间也无显著差异。

论:术中辅助使用右旋美托咪啶输注(0.2–0.8 µg · kg–1 · h–1),能减少芬太尼的用量、抗呕吐治疗和在PACU的停留时间 。对后期复苏(例如,肠功能恢复)或提高病人的整体复苏质量无显著作用。当减肥手术中使用右旋美托咪啶推荐输注率为0.2 µg · kg–1 · h–1,以尽量减少心血管副作用的风险。

(张燕 陈杰 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激酶抑制剂可增强丙泊酚对大鼠支气管平滑肌收缩的抑制作用

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:气管平滑肌收缩不仅由细胞内[Ca2+]增强引起,收缩肌兴奋也可增强同一[Ca2+]i的电紧张。小G蛋白RhoRho激酶(ROCK)在Ca2+敏感性调节方面起重要作用。在这项研究中作者研究了三种ROCK抑制剂(fasudil,Y-27632,H-1152)对鼠支气管平滑肌收缩的效果及ROCK抑制剂对丙泊酚引起的支气管效应的影响。

方法:雄性Wistar老鼠的肺内支气管环置于400ul含克-汉二氏溶液的器官浴用剂中,在给予30uM乙酰胆碱获得稳定的收缩后,(1)累积使用丙泊酚(1Um -1mM);(2)累积使用Y-276320.01-300uM),法舒地尔(0.01-100uM)或H-11520.01-100 uM);(3)累积共用丙泊酚(1Um-1mM)与Y-27632,法舒地尔或H-11520.03Um0.1uM)。

结果:1)丙泊酚可产生浓度相关的鼠支气管平滑肌舒张,(2)所有的ROCK抑制剂可产生浓度相关的舒张,(30.03uMY-27632与法舒地尔对丙泊酚的浓度反应曲线没有明显影响,而0.1uM时两种试剂可以使浓度反应曲线明显左移并降低EC50H-11520.03Um0.1uM)都可明显使丙泊酚的浓度反应曲线左移并降低EC50

结论:ROCK抑制剂,尤其H-1152能减弱支气管平滑肌收缩,ROCK抑制剂与丙泊酚合用可产生更明显的松弛作用。

(潘钱玲 陈杰 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-氧化亚氮的全身麻醉下剖腹产手术中时BIS值的研究:初产妇和经产妇的比较。

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:选择性剖腹产手术中呼气末1%七氟醚与50%氧化亚氮联合麻醉BIS值>60时,会增加术中知晓风险。作者假设七氟醚-氧化亚氮全身麻醉中经产妇的BIS值比初产妇低。

方法:有40例剖腹产手术的病人参与了本研究。一组是有急诊外科手术史的经产妇(经产妇组,n20),另一组是即行手术的初产妇组(对照组,n20)。麻醉诱导用硫喷妥钠4mg/kg,琥珀胆碱1.5mg/kg 1 %七氟醚和50 氧化氧氮混合氧气维持麻醉。评估并比较组间BIS值,收缩压,心率,血浆应激激素的浓度, Apgar评分及术后镇痛效果。

结果:在插管和分娩中经产妇的BIS值均较对照组低(p0.001)。两组患者血浆中去甲肾上腺素浓度均较基础值增加。经产妇组基础值和分娩中都比对照组多。收缩压,心率, Apgar评分,外科手术的特点,和垂体后叶素和皮质醇激素的血浆浓度两组无显著差异。两组术后镇痛视觉模拟评分相似,经产妇组在术后第一个24小时消耗的镇痛药较少(p0.01

结论:七氟醚和氧化亚氮全身麻醉下剖腹产手术中经产妇的BIS值比没有分娩史的初产妇低,且术后镇痛药物的消耗量低。

(王腾 陈杰 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.

 

腹部大手术术后给予氯胺酮可降低吗啡用量:一项前瞻性、随机、双盲、对照研究

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:氯胺酮可降低术后吗啡用量,但其最佳剂量和持续应用时间仍不清楚。在这项研究中,作者比较术中或术后48小时内给予氯胺酮对吗啡用量的影响。
方法: 81例接受腹部手术的患者随机、双盲分为三组: 1 PERI组术中及术后48小时接受氯胺酮(0.5 mg/kg+2 µg · kg–1 · min–1 ; 2 INTRA组仅术中给予氯胺酮(0.5 mg/kg注射后予2 µg · kg–1 · min–1 ; 3 )对照组给予安慰剂。记录术后48小时内吗啡用量,VAS评分及副作用(镇静评分,恶心-呕吐评分,恶梦,精神失常,或幻想)。

结果:术后24小时吗啡累积用量PERI(中位数 = 27 mg, 离散度= [19])显著低于INTRA(48 mg [41.5])和对照组(50 mg [21]) (P < 0.005)PERI组和INTRAVAS评分均明显低于对照组( P < 0.001 ), 对照组与PERI组相比恶心发生较高27 %与4 P= 0.005 。各组间镇静评分和精神失常无差别。
结论:术后48小时内给予小剂量氯胺酮可改善术后镇痛效果显著降低吗啡用量,而且恶心发生率较低并无副作用。

(陈伟 陈杰 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.

 

围术期使用加巴喷丁对整形外科病人鞘内注射吗啡引起的术后瘙痒症的保护作用

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:瘙痒是鞘内注射吗啡最常见的副作用。加巴喷丁是一种抗惊厥药,并且已经被证实对某些慢性瘙痒有一定的治疗作用。但是它用于鞘内注射吗啡引起的瘙痒的疗效还未进行评估。

方法:86名脊髓麻醉下行下肢手术的病人随机、双盲分为两组,术前2小时分别给予1200mg的加巴喷丁或安慰剂。所有的病人都鞘内注射0.5%的布比卡因15mg和吗啡0.2mg。在鞘内注射吗啡后3691224h观察是否发生瘙痒。

结果:对照组较加巴喷丁组出现瘙痒的病人多(77.5%vs47.5%P=0.01)。加巴喷丁组患者发生瘙痒的时间较对照组患者推迟。鞘内注射吗啡3h6h后瘙痒的严重程度试验组较轻。

结论:术前给加巴喷丁能防止下肢手术病人鞘内注射吗啡引起的瘙痒。

(王鹏 陈杰 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受体的表达及对NMDA受体离子流的调节作用

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受体的存在仍然有争论。该水平的NMDA受体激活后兴奋性增强,临床上表现为痛觉过敏。已有研究显示大鼠纹状体神经元A2A受体激活后抑制NMDA受体的离子流。在本研究中,作者在大鼠脊髓腰段背角第二薄层神经元内寻找腺苷A2A受体,并研究A2A受体激活后能否调节NMDA受体的离子流。

方法:试验在大鼠脊髓腰段进行。脊髓腰段内的腺苷A2A受体转录体通过RT-PCR技术测定。同时也做Western blot试验。RT-PCR技术还专门用于第二薄层,且第二薄层神经元内腺苷A2A受体转录体通过单细胞RT-PCR技术检测。腺苷A2A受体激活后对NMDA受体的作用通过全细胞结构膜片钳技术研究。

结果 RT-PCR显示在脊髓腰段存在腺苷A2A受体转录体。Western blot试验揭示了A2A受体存在于脊髓腰段。在脊髓胶质进行的RT-PCR也显示了腺苷A2A受体转录体的存在。最后,单细胞RT-PCR也显示腺苷A2A受体转录体存在于第二薄层神经元的标本中。膜片钳的结果表明应用选择性A2A受体激动剂可抑制NMDA受体的离子流。

结论:这些结果证明A2A受体存在于大鼠脊髓腰段背角胶质的神经元内,并且通过应用选择性A2A受体激动剂抑制NMDA介导的离子流。因此,A2A受体的配体能够调节在脊髓水平的疼痛传导过程。

(赵燕星 陈杰 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.

 

伏核内多巴胺D2样受体与氧化亚氮(N2O)的镇痛作用

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的抗伤害机制还未完全阐明。另一方面,许多研究表明与记忆及强化过程有关的中脑边缘系统多巴胺能神经元在脊神经索镇痛系统中有重要作用。作者假设中脑边缘多巴胺能系统与N2O的抗伤害作用有关。

方法:本研究应用成年雄性Fischer大鼠。为了检测多巴胺能系统是否是由N2O激活的,暴露于75%N2O的大鼠脑腹侧被盖区冰冻切片用双重染色的方法来检测c-Fos与酪氨酸羟化酶。为了鉴定多巴胺能系统是否与N2O的抗伤害作用有关,应用生理盐水或雷氯必利(多巴胺D2样受体拮抗剂)注射到伏核壳(NAc)区域。在暴露于25%氧气75%氮气或25%氧气75%N2O30min后大鼠接受福尔马林试验,并用免疫组化方法检测其脊髓。

结果:暴露于75%N2O增加脑腹侧被盖区酪氨酸羟化酶阳性细胞内c-Fos表达。福尔马林试验显示伏核壳(NAc)区注射雷氯必利减弱了N2O的抗伤害作用,且阻断了N2O对脊髓背角福尔马林诱导的c-Fos表达的抑制作用。

结论:吸入N2O可能激活中脑边缘多巴胺能神经元,而且N2O的抗伤害作用至少部分是由伏核壳(NAc)区域的多巴胺D2样受体介导的。

(张江玲 陈杰 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.

 

经皮吹入氧气并不能改善心脏手术病人胸骨伤口的氧合

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:心外科手术中,胸骨伤口裂开和感染的发生率为1%。组织氧压(PsqO2)是术后感染的主要危险因素,伤口裂开患者的的组织氧压一般较低。我们研究该假设,在心外科手术病人中经皮供氧是否可以改善胸骨伤口的氧合。我们的第二个假设是,额外吸氧是否可以改善伤口的PsqO2

方法:心肺分流术后,30名患者随机分组,接受治疗(12 EpiFlo 氧发生机(Ogenix, Inc., Beachwood, OH)6 mL/h向封闭的包裹伤口内供氧或(2)不给予上述治疗。测定伤口下{approx}5 mm处的 PsqO2 和温度。在给予氧疗(Fio2 = 60%)1h 测定PsqO2 和动脉氧分压 (Pao2),在监护室的第一天和第二天早上随机分两组供氧,Fio2 分别为30%50%

结果:由于技术问题,4名病人出组。病人的基本情况、手术类型和围手术期处理在各组基本一致。增加Fio2 30% 50% 可以改善 Pao2 99 [84–116]149 [128–174] mm Hg (P < 0.001, mean [95% CI]) ,胸骨伤口的 PsqO223 [16–33]27 [19–38] mm Hg (P < 0.001).相比较,局部吹入氧气,组织的氧合没有明显改善:前后分别为24 [14–41] 25 [16–41] mm Hg (P = 0.88)

结论:额外的增加吸入氧气可以改善心肺分流术后Pao2和胸骨PsqO2 ,从而降低感染的风险。然而,向封闭的包裹伤口内供氧并不能有效改善伤口 PsqO2 ,因而并不能有效降低心脏手术后胸骨伤口处的感染。

(章一静译,薛张纲校)

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.

 

 

对新生儿大脑的神经保护对策

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.

 

围产期大脑的损伤是儿童时期死亡和终生残废的首要原因。脑性麻痹和认知缺损通常是由于室周围白质损害,主要见于32周胎龄前出生的婴儿;而皮层皮层下的损害主要发生于足月儿。虽然近来在新生儿监护方面有所进步,但是对围产期的脑损伤仍没有有效的治疗方法。几种干预措施,例如硫酸镁用于早产新生儿,低体温用于足月儿,是已完成的或正在进行中的临床试验的焦点。正如这篇综述所讨论的,对围产期大脑损伤的病理生理学机制的改良认识有助于识别神经保护干预措施的潜在的靶位。

(宣丽真译 薛张纲校)

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.

 

 

小计量异丙酚引起乳鼠大脑神经元凋亡

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.

 

可阻断NMDA受体或者激动GABA-A抑制受体的药物具有引起发育中啮齿动物大脑神经元凋亡的作用。异丙酚曾被报导对上述两者均有影响,但并未充分证实可引起发育中的神经元凋亡。我们假定满足一只乳鼠接受外科手术麻醉的腹膜内给药剂量是200 mg/kg。然后我们将异丙酚剂量进行分级(25–300 mg/kg i.p.),发现≥50 mg/kg的剂量可引起显著的神经元凋亡。由此我们得出结论,1/4手术麻醉剂量的异丙酚即可引起乳鼠大脑神经元凋亡。

(夏俊明译 薛张纲校)

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.

 

术前口服Passiflora减轻门诊病人的焦虑:一项双盲,安慰剂控制的研究

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:许多术前手术的病人有焦虑症状,因此研究一种术前使用的能减轻焦虑而又对精神运动损伤最轻的药物是很必要的。

方法:在该研究中60名研究对象被随机等分成两组,分别于术前90分钟口服西番莲属翘摇苷(500 mg, PassipyTM IranDarouk)和安慰剂。于服药前,服药后10, 30, 60,90分钟都对每名患者的焦虑和镇静状态予以评估,该评估以量化测试的方式进行。在病人进入手术室,拔管后3090分钟对精神状态予以评估,该评估采用Trieger Dot 测试和Digit-Symbol 替代测试。每名患者从进入PACU到离开的时间间隔被记录下来。

结果:两组病人的人口统计学特征,ASA分级,手术时间,基础NRS评分,在预设时间内的镇静状态,离开时间都差不多。口服西番莲属组的NRS焦虑评分明显低于对照组(P < 0.001)。两组在PACU里的心理状态和精神运动功能恢复情况没有太大差别。

结论:门诊手术的病人术前口服西番莲属可以减轻焦虑而不产生过度镇

(孙鹏飞译 薛张纲校)

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.

 

 

在人低剂量吸入七氟醚后可以减少粒细胞-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:七氟醚是有内皮保护作用的镇静镇痛的药物,我们在人体试验了吸入低剂量的七氟醚是否可以持续抑制粒细胞-血小板激活的副作用。

方法:10名健康的成年男性志愿者参与了这项研究。每人吸入 0.5–1 %的七氟醚1h,吸入氧浓度为50 vol %。单纯吸入50%额氧气为对照组。 分别在试验前、吸入七氟醚即刻、吸入七氟醚24h三个时间点抽取静脉血,通过流式细胞仪测定粒细胞和血小板表面分子标志物 (CD41, CD42b, CD62P/P-selectin, and PAC-1),通过血栓弹力图评估白陶土诱导的血栓形成。在流式细胞仪的试验中,血小板被花生四膝酸(AA, 30 µM),氯喹腺苷 (ADP, 1 µM)和凝血酶受体激肽(TRAP-6, 6 µM)刺激。

结果:AA, ADP,TRAP-6增加了血小板CD42b的表达,而CD62PPAC-1的表达下降。受到刺激,粒细胞和血小板的聚集增加。相比于对照组,低剂量的吸入七氟醚24h后可以降低 ADP诱导的血小板CD62P 的表达,在124h后减少因AAADP刺激引起的粒细胞-血小板聚集物的形成,以及在24h后减少TRAP-6的这个作用。 相比于对照组,吸入七氟醚24h后减少粒细胞-血小板聚集物的形成以及减少伴随的血凝块形成的作用持续存在。

结论:我们在第一时间证明了,低剂量的吸入七氟醚(<1 %)后24h可以减少粒细胞-血小板的激活以及伴随的血栓和形成。

(施颖译,薛张纲校)

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.

 

 

延长使用异氟醚、丙泊酚、右旋美托咪定、氯胺酮对于成年鼠神经细胞增殖的影响

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:最近有证据表明,成年动物海马区新神经元的增殖对于学习、记忆等认知功能有着重要作用。在动物个体中,神经元的增殖受着年龄增长、GABA受体活动、基底前脑电活动、脑组织去甲肾上腺素水平降低、环境刺激减弱这些因素的抑制。这些情况与麻醉过程的相似提示我们,麻醉过程可能会调整新细胞的增殖,甚至由麻醉引起的成年动物神经细胞生长抑制会引起术后认知功能障碍。为了检验这种假设,我们研究了四种麻醉药物的延长麻醉对于年幼及年长大鼠的海马区神经细胞增殖的影响。

方法:年幼(约3月龄)以及年长(约12月龄)的雄性Sprague-Dawley鼠,用四种(异氟醚、丙泊酚、右旋美托咪定、氯胺酮)之一的麻醉剂麻醉8小时,大鼠采用自主呼吸,麻醉剂的浓度以正向反射消失以及能耐受夹式血氧检测仪来滴定。暴露于麻醉剂6个小时时,给予大鼠腹腔内注射200mg/kg的溴脱氧尿苷(bromodeoxyuridine,BrdU),数小时后处死。收集其海马部位的冰冻切片,使用免疫酶标技术来测定其BrdU浓度,计数齿状回的BrdU阳性细胞数,并与未麻醉的对照组相比较,以此给细胞增殖分级。年幼大鼠组四种麻醉剂都使用。年长大鼠只使用异氟醚和氯胺酮,并且在晚上吸入异氟醚。

结果:共有年幼大鼠42只,中年及老年大鼠26只参加实验。与对照组相比,年幼大鼠中使用任一麻醉剂的延长麻醉对于BrdU阳性细胞计数并无影响。年长大鼠中,在白天吸入异氟醚8小时对于BrdU标记亦没有影响。年长鼠与年幼鼠相比较,BrdU阳性细胞数显著较高。年长鼠中,氯胺酮麻醉者与对照组相比较,BrdU阳性细胞数降低26%。年长鼠在晚上吸入异氟醚8小时者与未麻醉的对照组相比,BrdU标记并无明显差异。

结论:即使使用了多种的、不同的麻醉药物,我们发现延长麻醉对于年幼大鼠的海马区细胞增殖并没有什么影响;而氯胺酮麻醉对于年长鼠的海马区细胞增殖有轻微的抑制作用,且异氟醚麻醉并未发现昼夜节律影响。这些数据都表明,麻醉剂似乎并不能影响神经细胞的增殖。更进一步的说,麻醉剂诱发的细胞增殖抑制作用在术后认知功能障碍中并不是主要角色。对比思考我们的实验发现,以及现有的对于麻醉剂作用过程的理解,和已知的细胞增殖修饰基因的了解,我们得到了一个并不完整的认识,来解释究竟是什么因素在神经元细胞的增殖中起了药理学和行为学层面的关键作用。

(秦敏菊译 薛张纲校)

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.

 

 

评判手术病人外周血细胞比容的应用:不能很好反映真实血细胞容量

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:外周血细胞比容一般被用来作为是否输血的指标。但对于手术病人来说,改指标并不能有效反映真实的红细胞含量。我们比较了外周血细胞比容与以下三方面的关系:(1)血浆容量,(2)估计循环血容量,(3)标化的血细胞比容与它们的关系。

方法:我们使用了BVA-100血容量分析仪(Daxor Corporation, New York City, NY)评估了入外科监护室的病人的情况。血浆容量直接通过连续标记白蛋白浓度来测定。红细胞容量通过血浆容量和外周红细胞比容计算而得。所有容量指标使用标化百分比含量表示。通过Metropolitan寿命表中的理想体重经公式计算得到理想容量。外周血细胞比容与标化的血细胞比容相比较,从而判断该指标是否可以反映正常的血容量

结果:从40名平均年龄在61 ± 20岁的病人处获得了86个数据,这些病人的ASA评分II级得分20 ± 6,死亡率为13%。入院的主要原因是严重的败血症 (n = 11),出血性休克(n = 7),呼吸衰竭(n = 20)和心脏衰竭(n = 2)Bland–Altman分析显示标准和外周血细胞比容的平均差值是3.4 ± 7.895%的置信区间是1.7–5.148%的外周血细胞比容低于标化血细胞比容 17%的外周血细胞比容高于标化血细胞比容,两者一致的为 35%

结论:外周血细胞比容可能不能准确得反映手术病人血细胞含量。这个结论需要更大样本的手术病人通过比较双重同位素技术来验证。

(刘婷洁译,薛张刚校)
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%.

 

 

对血管内皮生长因子在严重脓毒症及脓毒性休克中的研究

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:已有研究显示在严重脓毒症中,血管内皮生长因子(VEGF)的水平有所增高。我们通过对患有严重脓毒症的成年病人的VEGF水平的观测,以研究其在预知发生脏器功能不全及院内死亡率中的作用。

方法:我们在芬兰的24个多学科重症监护室(ICU)中设计了一个前瞻性的观察性队列研究,所有这些入住ICU的病人(共4500人)均为在2004.11.12005.2.28期间以严重脓毒症的标准进行过筛选,若他们符合严重脓毒症的诊断标准则予选择入组。

结果:其中有470人符合严重脓毒症的诊断标准。在获得知情同意后,我们留取了250位病人在入组当时(第0天)的实验室血样,以及215位病人在入组后72小时的血样,再将这些血样与30位健康个体的血样比较。我们获得在ICU内的死亡率为13.2%,院内死亡率为26%;并测得在0天时的血清VEGF的中值为423 pg/mL (其四分位数区间 [IQR] 159858 pg/mL),而在72h时的血清VEGF的中值为521 pg/mL (其四分位数区间 [IQR] 1821092pg/mL),而两者均高于健康对照组(P值分别为0.0290.003)。低水平的血清VEGF浓度多与更严重的(持续脏器衰竭评分为3-4,高于0-2分者)肾衰及血液学功能障碍有关,且在死亡患者中其0天及72h时的血清VEGF浓度则明显低于存活者(P值分别为0.01<0.01)。但通过受试者工作特性曲线分析显示,在0天及72h的血清VEGF浓度的曲线下面积分别为0.58 and 0.63(而其95%的可信区间分别为0.48-0.680.54-0.72, P值分别为0.10.009)。

结论:血清的VEGF浓度在严重脓毒症患者中有所增高,而低水平的血清VEGF浓度则多与血液学及肾功能障碍相关。我们虽可知死亡患者的血清VEGF浓度低于存活者,但将它作为严重脓毒症患者院内死亡率的预测依据尚不够充分。

(刘沁译 薛张纲校)

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.

 

抗惊厥药物的抗伤害性作用小鼠内脏疼痛模型

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:在多种神经病理性疼痛和炎性躯体疼痛模型中,有证据表明酰胺咪嗪、奥卡西平、加巴喷丁和托吡酯有抗伤害性刺激的作用。但这些资料都未表明此类药物对内脏痛的潜在作用。该研究中,我们用扭体试验作为小鼠内脏痛的模型研究和比较了酰胺咪嗪、奥卡西平、加巴喷丁和托吡酯的作用。除此以外,还检验了这些药物对运动状态的影响以比较用于治疗急性内脏痛的耐受性。

方法:用乙酸扭体试验评价抗惊厥药物的抗伤害作用。用旋转试验测试其副作用。

结果:口服酰胺咪嗪(25–60 mg/kg 、奥卡西平(10–40 mg/kg )、加巴喷丁(10–70 mg/kg )和托吡酯(5–30 mg/kg )后,在扭体试验中会使小鼠翻腾次数以剂量依赖的方式减少。在旋转试验中,酰胺咪嗪(60–140 mg/kg、奥卡西平(20–450 mg/kg)口服后会使小鼠旋转时间以剂量和时间依从性方式明显下降。使用最大剂量时,加巴喷丁(1000–2000 mg/kg和托吡酯(400–1500 mg/kg)不会明显影响小鼠的运动功能。酰胺咪嗪、奥卡西平、加巴喷丁和托吡酯的治疗指数(运动影响TD50/翻腾ED50)分别是>148.5>60.215.22.3

结论:这些结果提示,在小鼠扭体试验模型中使用酰胺咪嗪、奥卡西平、加巴喷丁和托吡酯能有效地对抗伤害性刺激。在一定剂量范围不会对运动产生影响。托吡酯是最有效和最易耐受的药物。

(蒋宗明译 薛张纲校)

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.

 

 

一项关于可乐定和腘窝神经组织阻滞后镇痛持续时间的随机、双盲、安慰剂对照研究

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:测试将100 µg可乐定加入0.375%布比卡因 溶液中将延长腘窝神经组织的镇痛时间的假说。

方法:选取99名入院拟行足部或踝部手术的术后患者进入随机、双盲、安慰剂对照研究队列。使用30ml加入肾上腺素的0.375%布比卡因溶液为患者行腘窝神经阻滞。患者行腘窝神经阻滞时被随机分为:不含可乐定的布比卡因组,100 µg 可乐定肌注组或含100µg可乐定的布比卡因组。患者同时采用腰硬联合麻醉,隐神经阻滞,术后行病人自控静脉镇痛。评价指标为病人报告的镇痛持续时间。

结果:可乐定阻滞组的镇痛持续时间延长有统计学意义(含可乐定的布比卡因组为18 ± 6小时,可乐定肌注组为14 ± 7小时,对照组为15 ± 7小时,含可乐定的布比卡因组与对照组组间P = 0.016)。组间疼痛评分,镇痛药用量及镇痛治疗相关的副反应无差异。

结论:可乐定可明显延长布比卡因腘窝神经阻滞的镇痛持续时间。

(黄凝译  薛张纲校)

 

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.

 

低体温和酸中毒对人全血的凝血有协同损害作用

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:各种不同的临床设计报道了低体温和酸中毒对凝血障碍的影响。我们评估了全血的凝血来确定低体温和/或酸中毒对止血的作用。

方法:来自10名健康志愿者(2女,8男)的全血样本(3.000µL),加入40µL摩尔浓度增加的盐酸酸化以达到血pH(α-pH固定计)介于7.07.37之间。用本质(InTEM TM)和非本质(ExTEM TM)活化测定法孵化30分钟后,再用旋转血栓弹性测定法分析凝血功能。为了评估温度依赖性作用,所有试验均在血液/血栓弹性测定仪的温度30333639°C下分别进行。此外,通过添加细胞松弛素D进行了一项额外的非本质活化试验,来检测无血小板作用下的凝块构成。

结果:正常pH下的低体温导致了凝血时间延长[ExTEM: 65 s ± 3.6 (36°C)85 ± 4 (30°C), P < 0.001; 凝血时间, InTEM: 181 s ± 10 (36°C)226 ± 9, P < 0.001],凝块形成时间延长[ExTEM: 105 s ± 5 (36°C)187 ± 6 (30°C), P < 0.001; InTEM: 101 s ± 5 (36°C)175 ± 7, P < 0.001],并且伴有α角的缩小,[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]。最大凝块硬度仅在InTEM测定法中显著受损[56.9 mm ± 0.9 (36°C)52.7 ± 0.9, P < 0.05]。相反,正常体温下酸中毒本身无明显影响。酸中毒放大了低体温的作用,并在本质和非本质活化测定中协同性损害凝血时间、α角并减小最大凝块硬度。用细胞松弛素D消除血小板功能后进行的纤维蛋白凝块形成试验显示没有受损。在低体温和/或酸中毒环境下凝块溶解减少,而在高体温下增加。

结论:在此次体外研究中,血栓弹性测定法显示:酸中毒使低体温引起的凝血改变恶化,而不伴低体温的酸中毒对凝血无显著影响。这种效应是由对凝血因子和血小板功能的抑制介导的。因此,37°C下进行的血栓弹性测定法高估了低体温尤其伴酸中毒时凝血功能的完整性。

(唐李隽    马皓琳  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.




全身麻醉药对脑结构发育和神经认知功能的影响

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:近来有研究发现全身麻醉药可以导致一些非成熟动物模型的神经元细胞死亡。全世界每年有几百万的儿童在外科手术或放射检查过程中用到挥发性麻醉药,所以麻醉药在新生儿或婴儿诱发神经毒性的可能性在小儿麻醉的安全性方面引发了极大的关注。但是,将动物研究资料应用于临床麻醉实践仍存在不确定性。在本综述中,我们评估了常用麻醉药对人类和动物新生儿神经结构和神经认知功能影响的证据。

方法:在医学数据库,包括MedlineCinahlPubmed、美国麻醉医师协会、国际麻醉研究协会、儿科麻醉协会和神经科学协会的年会摘要以及个人文件中查询关于麻醉诱发神经毒性的资料。

结果:越来越多的研究发现多种麻醉药可以使未成熟动物模型的神经结构发生变性。一些研究显示动物在新生儿时期接受过麻醉,成年后有认知功能损害。目前还没有前瞻性研究可以评估新生儿时期接受过麻醉后的儿童的神经认知功能。但是,一些回顾性综述表明幼儿长时间麻醉后有暂时性的神经学后遗症,且较大的研究认明新生儿手术和麻醉后有长期的神经发育损害。

结论:动物模型中麻醉诱发神经变性的证据是令人注目的。虽然未在幼儿中前瞻性研究过这个现象,无对照的资料已经表明在生命早期接受过手术和麻醉后可能会有神经功能损害。倘若对公众卫生有严重的含义,就必须在实验室动物和幼儿中对这个现象进一步研究。

(张莹译  马皓琳 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.


右美托咪啶经鼻给药与口服咪达唑仑在小儿麻醉术前用药中的比较:一项双盲随机对照试验

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:咪达唑仑在小儿术前用药中最为常用。在麻醉诱导时它比父母在场或安慰剂在减轻焦虑、增加顺从性方面更有效。已有研究提出{alpha}2 受体激动剂可乐定是一种替代药品。右美托咪啶比可乐定有更强的{alpha}2 受体选择性,且药代动力学性质更有利。我们设计了这个前瞻性、随机、双盲、对照的试验来评估右美托咪啶经鼻给药在小儿术前用药中应用是否和口服咪达唑仑一样有效。

方法:96ASA I~II级择期小手术的患儿随机分为3组。M组术前口服咪达唑仑0.5 mg/kg(对乙酰氨基酚糖浆中)并经鼻给安慰剂。D0.5组和D1组分别经鼻给右美托咪啶0.5 1 µg/kg,以及对乙酰氨基酚糖浆。由一名研究者记录患者镇静状态、行为评分、血压、心率以及氧饱和度直到麻醉诱导。还记录恢复特征。

结果:三组在父母分开可接受度、诱导时行为评分和苏醒行为评分均无差异。D0.5组和D1组与M组相比,在与父母分开时更为镇静(P < 0.001)D1组的患者在麻醉诱导时明显比M组镇静(P = 0.016)

结论:右美托咪啶经鼻给药比口服咪达唑仑产生更多的镇静作用,但合作性相似并可接受。

(朱 慧译 马皓琳 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.



补充供氧能否减少术后恶心呕吐?随机对照实验的荟萃分析

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

背景关于补充供氧降低术后恶心呕吐(PONV)发生率的能力是不一致的,最初的研究表明它对减少PONV是有益处的,而随后的试验证明它不能减少PONV

方法:为了弄清补充供氧是否是减少PONV的一种有效和可靠的方法,我们对比较了围手术期80%吸入氧浓度和 30%–40%吸入氧浓度影响PONV发生率的随机对照试验进行了系统回顾(MEDLINECochrane图书馆、手工查找和文献目录,无语言限制,到20063月为止)。对本次系统回顾而言,PONV被定义为术后24小时内的任何恶心、干呕和/或呕吐。观察的终点为早期PONV(0–6 h)、后期PONV (6–24 h)和总的PONV (0–24 h)。我们的荟萃分析包括了10个试验的共1729名病人的数据:860名病人的吸入氧浓度为80%,另外869名病人的吸入氧浓度为30%–40%

结果:在吸入氧浓度为80%的病人中,发生早期、后期和总的PONV的相对危险度(95%可信区间)分别为0.91 [0.71–1.16]0.88 [0.69–1.11]0.91 [0.77–1.06]。对于早期、后期和总的恶心呕吐的发生率的结果是相似的。

结论:最初的两个研究表明给病人吸入浓度为80%的氧气可以降低PONV的风险,但是这个阳性结果没能被随后的任何试验证明。鉴于所有的可得到的证据,80%的吸入氧浓度不应该被再认为是减少总的PONV的一种有效或可靠的方法。

(吴进   马皓琳 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.



芳香族麻醉药对伤害性刺激引起的背角神经元反应的作用

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强γ-氨基丁酸A型受体和/或抑制N-甲基-d-天冬氨酸(NMDA)受体。本研究假设抑制背角神经元对伤害性刺激的反应与苯酚(BNZ)、o-二氟联苯和六氟苯(HFB)对NMDA受体作用的强度相关。

研究方法:大鼠在地氟醚麻醉下行T13-L1椎板切除术,细胞外记录腰段脊髓神经元活性。停止给予地氟醚后确定每个芳香族麻醉药的MAC。然后给予脊髓背角伤害性感受神经元在后爪的感受野一个长达5s的伤害性机械刺激并记录0.8MAC1.2MAC时单个神经元的反应。同样,对接受BNZHFB的去大脑大鼠在0–1.2 MAC时记录这些反应。

研究结果:完整的大鼠中,BZNo-二氟联苯和HFB在围MAC范围内浓度增加,其抑制背角神经元对伤害性刺激的反应与这些药物离体阻断NMDA受体的强度直接相关。去大脑大鼠中,1.2 MAC BNZ对伤害性感受反应的抑制达60%,且从0.8MAC1.2MAC神经元对伤害性刺激反应百分比进一步减少,近似于在整体大鼠中的发现。在去大脑大鼠中,HFB 引起剂量相关的MAC渐进性减少(最多减少25%),但是在整体大鼠中,MAC0.8增加至1.2使得神经元反应(非显著性)增加。

结论:在整体大鼠中的发现提示氟化芳香族麻醉药抑制背角神经元对伤害性刺激反应的作用机制与NMDA受体阻断有关。上述结果结合在去大脑大鼠中的发现提示HFB的脊髓上效应(可能作用于γ

 

 
-氨基丁酸A型受体)可能对伤害性感受有易化作用。

(周雅春 李士通 马皓琳 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.


局麻药氨苯丁酯抑制PC12细胞中总的和L-型钡电流

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:氨苯丁酯或称n-丁酰基-p-氨基苯甲酸酯是一种长效的实验用局麻药,硬膜外悬浮液注射用于治疗慢性疼痛的治疗。我们研究了Cav1.2/L-型钙通道是否可能为氨苯丁酯的这种作用的一个靶位。

方法:用全细胞膜片钳技术(电压钳)在未分化的大鼠PC12细胞上研究氨苯丁酯对这些通道的作用。Ba2离子被用作钙通道电流中的载荷子,而使用不含K的溶液以排除K电流。

结果:500 µM的氨苯丁酯可逆性地抑制90% ± 3%(n = 15)的全细胞总钡电流,而10 µM的硝苯吡啶抑制75% ± 7% (n = 6)的这种钡电流。预暴露于氨苯丁酯继而洗脱可将硝苯吡啶的抑制作用减至47% ± 5% (n = 10)。这些抑制作用与测量方法以及溶液中的药物赋形剂(低于0.1%的乙醇;n = 6)无关。

结论:氨苯丁酯抑制PC12细胞中通过表达的钙通道型的总钡电流,包括Cav1.2/L-型通道。由于Cav1.2通道也可存在于人的伤害感受性C纤维,这一结果使得这些L-型通道可能与氨苯丁酯的镇痛作用有关。

(黄施伟 译,马皓琳 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.




游离皮质醇在败血症及感染性休克中的应用

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:严重败血症可以通过激活下丘脑垂体轴来增加皮质醇的产生。在一些研究中,基于促肾上腺皮质激素刺激试验或皮质醇基础测量值来开展的氢化考的松替代治疗已改善了结果。因为只有皮质醇的游离部分是有活性的,在危重病人中测定游离皮质醇可能比监测总皮质醇更有意义。我们测定了严重败血症患者的总皮质醇及游离皮质醇并将其浓度与预后作了相关分析。

方法:在一项前瞻性研究中,严重败血症患者的定义按照美国胸外科医师学会/危重病医学会的标准。研究开始后的24小时内抽取血样。使用电化学发光免疫分析法测定血清皮质醇。并使用Coolens法计算血清游离皮质醇的浓度。

结果:收集125位患者的血样,其中62位为严重败血症,63位为感染性休克。医院死亡率为21%。血清游离皮质醇计算值与血清总皮质醇浓度有很好的相关性(r = 0.90, P < 0.001)。败血症及感染性休克的患者总皮质醇浓度无差别(728 ± 386 nmol/L793 ± 439 nmol/L, P = 0.44)。死亡组血清游离皮质醇的计算值(209 ± 151 nmol/L)与血清总皮质醇浓度(980 ± 458 nmol/L),与存活组(119 ± 111 nmol/L 704 ± 383 nmol/L相比更高( P = 0.002)。根据定义,肾上腺功能不全的发生率从8%54%不等。

结论:临床上,对于接受皮质醇治疗的严重感染及感染性休克病人,游离皮质醇的计算值不能为鉴别病人提供基本信息。

(裘毅敏   马皓琳 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.

 

 

 

复杂区域疼痛综合征I型中血浆5羟色胺浓度升高

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:复杂区域疼痛综合征I(CRPS1)病人通过应用5-羟色胺2A受体拮抗剂酮色林能达到一些改善。我们测定CRPS1过程中5-羟色胺的血浆水平,比较这些水平与疾病特征的相关性。

方法:选择35例患CRPS13年的病人和35例年龄一致的健康对照,测定血浆5-羟色胺。

结果:血浆5-羟色胺水平分别是411 ± 263 nmol/L 29 ± 18 nmol/L (P < 0.001) 与疾病特性没有相关性。

结论CRPS1病人的血浆5-羟色胺水平明显升高提示在这一疾病的过程中5-羟色胺起着重要作用。然而,因为与独特的疾病特征缺乏相关性,5-羟色胺可能只是CRPS1的一系列介导剂中的一员。

(彭中美 马皓琳 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.


大鼠内吗啡肽的脊柱镇痛效应:行为和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:内吗啡肽-1和内吗啡肽-2µ型阿片类受体的高度选择性内源肽。但是,它们功能的效能和选择性还是有争论的。在此研究中,我们将鞘内给内吗啡肽-1和内吗啡肽-2对伤害感受分析及G蛋白活化的影响作用与一个高度有效的µ-阿片受体激动剂[d-Ala2,N-Me-Phe4,Gly5-ol]-脑啡肽(DAMGO)的这些作用作了系统性比较。

方法:用雄性斯普拉-道来大鼠制造急性和炎性疼痛模型,来比较抗痛效应的持续时间和强度。用激动剂-受激[35S]GTPγS结合来观察脊髓和丘脑膜中受体-G蛋白水平的机能活动。另外,用每个受体类型的选择性拮抗剂来验证大鼠脊髓中内吗啡肽的功能选择性。

结果:在急性疼痛模型中,鞘内注射后,内吗啡肽-1和内吗啡肽-2DAMGO产生较少的抗痛效应。DAMGO、内吗啡肽-1和内吗啡肽-2刺激的[35S]GTPγS结合的浓度-反应曲线显示,内吗啡肽-1和内吗啡肽-2DAMGO在脊髓和丘脑膜,产生较少的G蛋白激活 (即约50%–60%)。此外,鞘内注射内吗啡肽引起的抗痛作用被µ-阿片受体选择性拮抗剂纳曲酮阻滞(P < 0.05),但不会被δκ-阿片受体拮抗剂naltrindole nor-binaltorphimine所阻滞 (P > 0.05)

结论:内吗啡肽是G蛋白在脊髓和丘脑µ阿片受体活化的部分激动剂。体内和体外的测量结果都显示DAMGO比内吗啡肽更有效。脊髓内吗啡肽的抗痛效应可能在53%84%范围内,这依赖于伤害刺激的强度和模式。

(张曦 译,马皓琳 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.


镇痛药物曲马多可以起到辣椒素瞬时电位受体—1激动剂的作用

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:曲马多作为一种有效的镇痛药物被广泛应用于临床治疗。曲马多的作用机制主要表现在对µ型阿片类受体的激动作用,抑制神经递质再摄取,抑制伤害性疼痛系统的各种电压和配体门控离子通道。因为已有研究显示辣椒素瞬时电位受体—1(TRPV1, "辣椒素受体")可以起到痛觉中枢积分分子的作用,所以本次研究的目的是为了证实TRPV1在曲马多的复合作用机制中起的作用。

方法:为了达到实验目的,我们使用单细胞Ca成像技术和荧光成像平板分析测定中国仓鼠卵巢(CHO)细胞异源性过度表达TRPV1

结果:我们发现以下结果:(1)曲马多和辣椒素这个熟知的辣椒素受体激动剂一样,呈浓度依赖性地显著增加CHO细胞TRPV1内流钙离子;(2)该作用可以被TRPV1拮抗剂capsazepine 可逆性地阻止;(3)重复给予曲马多会造成显著的快速耐药性;(4)曲马多不修饰钙对照(无传病媒介表达)CHO细胞中的内流钙离子。

结论:总之,这些发现都强烈支持这一新奇而有趣的观念:曲马多可以起到TRPV1激动剂的作用。考虑到跟随着TRPV1对感觉神经元的激动作用之后的是血管神经肽的局部释放和传入神经纤维的显著脱敏作用(因此终止痛觉),我们的发现在解释曲马多的镇痛作用的同时也可以说明曲马多常见但“意外的”局部副作用(如引发灼痛和红斑)。

(姜旭晖 马皓琳 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.


电神经刺激或超声引导侧位矢状面的锁骨下阻滞:随机、对照、观察者单盲的比较性研究

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:超声引导经常用于锁骨下臂丛神经阻滞。这次研究中,我们比较电神经刺激和超声引导用于侧位矢状面的锁骨下阻滞。

方法80名患者,ASA1-2级,随机分成神经刺激组(NS组)和超声引导组(US组)。两组中的臂丛神经阻滞药物为0.6mL/kg甲哌卡因(15 mg/mL),含肾上腺素(2.5 µg/mL)。对于超声引导阻滞,局麻药从颅后注射到腋动脉。一位观察者在不知道阻滞方法的情况下评估阻滞并询问患者。阻滞成功的定义为肘部远端的所有五根神经出现无痛或者麻痹。主要的结果变量为麻醉到可以手术的时间、阻滞过程中量化的不适程度及止血带压迫缺血相关的疼痛数字评定量表(1-10)

结果NS组和US组的阻滞操作时间分别是4.3分钟 (标准差1.3)4.1分钟 (标准差1.3) (P = 0.64)。感觉阻滞的起效时间分别为13.7分钟 (标准差6.6)13.9分钟 (标准差5.8) (P = 0.99)。两组到可以手术的时间均为18.1分钟 (标准差分别为6.66.0) (P = 0.99)。与阻滞过程相关的不适度的中位数两组都是1 (P = 0.92),止血带疼痛的中位数NS0.5US1(P =0.32)。成功率NS85%US95%,两组之间没有显著性差异(P = 0.26)

结论:我们得出的结论是无论是用神经刺激还是超声引导来进行侧位矢状面的锁骨下阻滞都能取得良好的结果。使用超声引导使局麻药从颅后注射到腋动脉显得更有可行性。

(唐亮   马皓琳 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.