医学洗鉴录 - 主任大查房

血透和血滤的机理根本区别

amicacin@gmail.com(Amic) — Sat,31 Oct 2009 02:42:16 +0800

血透和血滤的机理根本就不相同，但决不是“加入的成分不同”：
血液透析是指溶质通过半透膜，从高浓度溶液向低浓度方向运动。血液透析包括溶质的移动和水的移动，即血液和透析液在透析器内借半透膜接触和浓度梯度进行物质交换，使血液中的代谢废物和过多的电解质向透析液移动，透析液中的钙离子、碱基等向血液中移动。比如：把白蛋白和尿素的混合液放入透析器中，管外用水浸泡，这时透析器管内的尿素就会通过人工肾膜孔移向管外的水中，白蛋白因分子较大，不能通过膜孔。这种小分子物质能通过而大分子物质不能通过半透膜的物质移动现象称为弥散。
弥散为血液透析的基本原理。

血液滤过是模仿肾小球的滤过功能、肾小管的重吸收和排泌功能，在滤过膜的血液侧加正压、在透析液侧加负压形成一定的跨膜压(<500mmHg)，使滤过率达到 60—90ml／分钟，将进人血滤器的水和溶质滤除(相当于肾小球滤过，但蛋白质和血细胞不能滤出)，同时补充人工配制的置换液(相当于肾小管重吸收)，以此保持水、电解质及酸碱平衡，使内环境稳定，每次置换液量应在20升左右。血液滤过主要依靠对流原理清除水分和中、小分子物质，对中分子毒物的清除效率显著高于血液透析。

由于他们的机制不同，所以“补充”或“交换”的液体成分要求也不尽相同。

术后早期炎症性肠梗阻

amicacin@gmail.com(Amic) — Mon,12 May 2008 14:09:46 +0800

术后早期炎症性肠梗阻(EPII)多见于手术范围广、创伤严重或已有炎症的病例，腹腔内有广泛粘连，剥离后肠浆膜层有炎性渗出，肠袢相互粘连，有些可能成角。故此类肠梗阻既有机械性因素，又有动力性因素，但无绞榨。EPII并非一种新型肠梗阻，只不过为突出其特征，称之为术后早期炎症性肠梗阻。
由于肠管高度水肿并致密粘连，甚至成脑回状，剥离时肠管浆膜广泛损伤渗血；EPII不是肠管某一处的机械性梗阻，为寻找梗阻部位而进行广泛的剥离，除造成更严重的肠管损伤和渗血，由于存在肠壁水肿，愈合能力差，肠蠕动功能断时间不能恢复等因素，极易造成肠瘘，且多为多处。而肠瘘是短肠综合征常见原因。

有关诊治参见《术后早期炎性肠梗阻的诊治》的笔记。
腹部手术后并发的肠梗阻有多种类型，术后不同时期发生的肠梗阻原因也不同。EPII约占术后肠梗阻的1/5。以前对其认识不足，寄希望于通过手术分离粘连解除梗阻。但此时肠管粘连广泛而严重或致密，高度充血水肿，脆性大极易损伤，绞窄可能性不大。反复手术不能解除梗阻，反而致EPII加重，使肠功能恢复期延长，甚至形成--肠瘘、短肠综合征。
[定义] early postoperative inflammatory ileus
EPII 发生于腹部手术后早期，是指由于腹部手术创伤或腹腔内炎症等原因导致肠壁水肿和渗出，形成的一种机械性与动力性同时存在的粘连性肠梗阻。在诊断EPII之前，必须排除机械性梗阻和继发于腹腔内或腹膜后感染、电解质紊乱等原因造成的麻痹性梗阻。
腹部手术创伤--广泛分离肠管粘连、长时间的肠管暴露以及其他由于手术操作所造成的肠管损伤。
腹腔内炎症--无菌性炎症，如腹腔内积血、积液或其他能够导致腹腔内无菌性炎症物质的残留。
[临床症状、诊断] 与其他肠梗阻有共同之处，即腹痛、腹胀、呕吐、停止排气排便。也有其明显特殊性。须注意动态观察。
1. 必须有近期腹部手术的病史。手术过程对胃肠道功能恢复影响较大，尤其是胃肠道手术、短期内反复手术、广泛分离粘连、肠排列、腹膜炎、异物或坏死组织残留以及其他造成肠管浆膜广泛受损的因素。
2. 多于术后1~2w内起病，尤其术后5~7d。典型EPII--术后可能有少量排气甚至排少许干便，但进食后即很快梗阻。
3. 腹痛、腹胀不如机械或麻痹性肠梗阻显著。多无高热。可为弥漫或局限性，取决于腹部手术和肠管受累的部位和范围，局限性多见于切口下方。
4. 腹胀多对称性，腹部膨胧但不如机械或麻痹性严重，无肠型或胃肠蠕动波。
5. 触诊柔韧感，各部不一，最显著部位即是肠管粘连最严重的部位，多于脐周或切口下方；无明显肠袢或包块。
6. 叩实音；听肠鸣音减弱、稀少或消失，无金属音或气过水声，梗阻缓解则肠鸣音恢复。
7. 全腹CT示：肠壁水肿、增厚、粘连以及肠腔积液积气，肠管均匀扩张和腹腔内渗出。同时有助于排除腹部其他病变如腹腔感染、机械性梗阻等。--有重要参考价值。
[治疗] 基本原则相同：禁食、胃肠减压和纠正内稳态。
特殊性：
1. 应用生长抑素--EPII初期，消化液分泌量可很大，其积聚肠腔，加剧肠壁水肿、肠腔扩张及水电解质紊乱，也影响肠功能恢复。
2. 正规全肠外营养支持（TPN）--EPII病程长（平均治愈时间约1个月），营养及内稳态难维持。TPN不仅是支持手段，使病人有条件等待病情缓解，更是一种重要治疗措施。①营养不良造成低蛋白血症，致肠壁水肿，影响肠功能恢复，增加体液从消化道丢失，甚至造成肠腔狭窄或梗阻。②有助于减轻术后高分解代谢，促进切口愈合纠正水电解质紊乱。
3. 应用肾上腺皮质激素--EPII是肠壁的无菌性炎症。激素可促进肠道炎症和水肿消退。通常地塞米松5mg iv Q8h*1W 逐渐停药。
4. 温盐水灌肠、洗胃--刺激胃肠蠕动，保护胃黏膜，清除肠腔积粪。
应用新斯的明--促进肠蠕动（腹部体征著缓但胃肠动力较差时）。
普瑞博思--促胃肠道排空（胃肠道恢复通畅后并维持到能正常进食）。
缓解标准：
①腹胀消失，排气排便。（梗阻缓解）
②尤其解水样便，--临床实践证实为重要指标。
③胃液著减、变清、不含胆汁；触诊由坚韧变为柔软；听诊肠鸣音由稀少变为活跃。
[预防]很多情况下，EPII是可预防的。关键是--提高对本病的认识！
1. 大量生理盐水冲洗腹腔（150ml/kg），清除其中的细胞因子、炎性介质、异物和坏死组织。--腹腔内任何异物（包括血液和组织碎屑）都能刺激腹膜单核巨噬细胞系统，产生大量细胞因子和炎性介质，造成无菌性炎症和肠管粘连。
2. 减少肠管损伤--手术中注意保护肠管，①避免钝性剥离。②尽量肠管浆膜化，消灭粗糙面。③多用湿纱垫，减少肠管暴露时间和面积，有助保护肠管浆膜面、减少不显性失水。④淘汰外排列，不宜滥用内排列。
3. 若术中腹腔污染严重或广泛分离粘连和其他原因估计会导致术后肠管广泛粘连时，应警惕EPII的可能性，对术后很早出现的排气应慎重对待，避免过早进食加重EPII。

--朱维铭，李宁。术后早期炎性肠梗阻的诊治。中国实用外科杂志，2000；20（8）：456~458

其他相关文献：
[1]朱维铭,李宁,黎介寿,尹路,任建安,顾军,姜军,王少华,王新波. 术后早期炎性肠梗阻的治疗[J]. 中国实用外科杂志,2002,(4).
[2]施宝民,王敬文,杨镇. 术后早期炎性肠梗阻的诊断与治疗[J]. 中国实用外科杂志,1999,.
[3]黎介寿. 认识术后早期炎症性肠梗阻的特性[J]. 中国实用外科杂志,1998,(7).

Technorati : 肠梗阻

何谓“重症监护”？

amicacin@gmail.com(Amic) — Mon,17 Mar 2008 10:27:39 +0800

这是黄教授的最新一片评论，其中的ICU的重症医学的“魂”的论述，个人颇为赞同，因为病人的危重阶段最常见的还是SIRS或者SEPSIS的状态及延续，2001年的时候在科里小讲课的时候，我就将其列为ICU的核心理论基础。也是我崇拜的一心想成为其学生的导师的主要研究放向。

何谓“重症监护”？

有朋友留短信，有版主发邀请......让谈谈我关于“重症监护”的想法。老实讲，我写不出已经发言的那几位仁兄的水平；此外，我看到大家都在籍图用自己的语言向别人证明自己认为的ICU就应该是比较理想的ICU的状况，其实ICU真的是什么，我想没有人能够给出终极的标准答案——1854-1856年南丁格尔（Nightingale F）在克里米亚战争（Crimean War）期间为严重负伤的士兵创建护理病区的时候，她不会前瞻地预计以及预计出当代护理医学（尤其危重护理）的发展走向；20世纪50年代荷兰Copenhagen的高级麻醉师Ibsen和同事组建全科式的急救病区以全力抢救脊髓灰质炎患者的时候不会想到这种形式就会是未来监护医学的雏形，更不会预见未来这个新的医学学科会和其他众多相关学科：麻醉学、急诊医学或者外科医学等等会有如此“深切”的纠结；1970年在美国加利福尼亚的心内科医生Max Harry Weil、麻醉医生Peter Safar和外科医生William Shoemaker等2 6位“仁人志士”创立美国危重症协会(Society of Critical Care Medicine, SCCM)时也不可能预计到21世纪的社会发展对“监护医疗”已经倚重到如此程度——80%的美国佬都有“重症监护”的体验，无论是作为患者、家庭成员亦或朋友。他们当初将危重病医学定义也只能是从原则上统领，不可能有进一步的限定了——“治疗危及生命的急性疾病或创伤的多学科医疗专业”（the multidisciplinary healthcare specialty that cares for patients with acute, life-threatening illness or injury），而SCCM则是一个多种专业、多种职业的，共同为确保和不懈地为危重症监护医学专业组作奉献的组织。到目前为止，我也想不出比上述概念更为具体的定义了——而正是这个定义足以令所有已从事或者准备从事这项职业的人陷入无尽的迷思（myth），尤其是在受到急诊科的竞争，外科佬的无礼，呼吸科的打压，神经内外科的夹击...等多种综合因素困扰之后，我们这种追根问底的病态就尤其明显。更兼国内学科建设时间不长，目前几乎没有纯监护医学成长背景的从业者，我们每一个人都有来自其他学科的医学从业经历，这更会令我们在比较“监护医学”与之前的“母体”时，更多的是流露出意味深长的暧昧眼神吧......

（题外话：试想再过50年，应该不会有学医的人再提出急诊与监护医学区别的问题了——关于监护医学本质的讨论很有点像目前此起彼伏的有关麻醉医生与麻醉护士职责的讨论，但职责问题迟早会解决的——在德国，麻醉护士是绝对不允许做任何接触到患者的任何操作，我想国内迟早也会这样，只是时间问题。这些问题的产生都或多或少都与学科成长初期的具体环境以及广泛存在的待遇问题有关，我想目前有关监护医学的讨论也并不是一个基于完全客观背景，甚至心情的的理论讨论。）

从监护医学的研究对象来看，固然所有危及患者的内稳态并存在生命危险的任何疾病都可以划归到监护仪学的诊疗范畴。不过我个人更倾向于“重症监护医学”的核心应该是以全身炎症反应综合征（Systemic inflammatory response syndrome，SIRS）和sepsis →严重sepsis和感染性休克→ALI/ARDS→MODS →生存或死亡为主链的（箭头不是确指序贯发生，这里只是一个metaphor），并在此基础上形成系统性生命支持的治疗体系。这条主干是所有危重病的共同通路，也应该是危重病专业最应该关注的临床线索。无论怎样命名监护医学或者加强治疗，亦或“深切治疗”，核心都应该是上面的主干，除此，别无其他。这也是本学科与其他学科的主要区别。也因为如此，在我看来，任何坚持以上述主干为医疗监护重点的病区就是抓住了重症医学的“魂”，它就是真正的“ICU”——无论它是以何种形式存在，也无论它从属于何种二级学科，更无论它是否配备了几台监护仪、呼吸机、肾脏替代治疗设备或者心外辅助装置...以上就是我截止2008年3月9号对监护医学的理解。我另外很欣赏的alonex所说的“ICU的核心是监护，支持，治疗的高度辩证统一。监护也是支持和治疗的一种形式”。

另一方面，我们必须认识到监护医学的出现与成长是社会发展和科学发展的综合产物，监护仪学简直就是管窥“社会制度体系（比如说医疗保险制度）”和“科学网络协作”的最佳范本之一。可见ICU运作良好或者监护医学发展顺畅是必须有良好社会制度和学科无间协作的双重保障的，否则监护医学的发展就有走向畸形之虞。依靠领导偏向、政策倾斜或者个人影响力都非良策，长远看也不可能培育不出优良学科成长的环境的，我想目前同行们对监护仪学发展的疑惑可能有些也是源于此吧。

监护医学的发展源自学科的扩散与交叉，我们在临床面对的也不是仅存在“sepsis”或“shock”临床表现的患者，这也决定监护医生的个人素质必须全面，不能是万金油，而应该比急诊医生更麻利，比内科医生更认症...更因此目前国际监护医学的发展倾向是在学科上更广泛交叉，但是在人员培养上却有收缩，强调体系内的全面培养，而不是分散到相关学科零散学习——根据SCCM相关工作组的意见，尽管目前尚无ICU运作的单一工作标准，但目前和未来都强调由危重症医生全面负责ICU内所有病人处置，其他科室医生仅作为会诊医生的“紧密”（Close）的工作模式。并以此为基础形成多种形式的组织形式。以我国监护医学现阶段的发展现状，重症学会成立不足3年的事实来看要实现体系内的自身良性发展恐怕还有难度，因此广泛利用其他学科已有的广泛资源不失为一种选择——映射到dxy，我觉得监护版的急诊或者内科病例不是多了，而是少了，不是要扼制，而是要扶持，问题是用何种形式更利于大家学习而已。

最后想说一下最近我的Blog上提到的“急诊监护化”的问题，我需要在这里廓清我的说法，避免被误引误用。首先“急诊监护化”是大势所趋。急诊医学不是监护医学，但不代表着急诊就只能是“分诊台”，尤其必要的监护和以监护为依托的“早期目标治疗”或者“集束化治疗”对于改善进入急诊的重症患者的预后有着重大意义的时候，我们就不能再象驼鸟一样逃避这个问题了。我觉得问题并不是急诊要不要成立监护室的问题，问题应该是急诊与监护中心的治疗交接和连贯的问题。但是，其次，“急诊监护化”并不等于急诊必须以“全程医疗”为己任：以德国和美国的急诊体系为例，急诊科都设有监护室，但是这些急诊室并不是以“治疗”为主要人任务的，而是以短期“诊断、监护和必要的基础治疗”为重点的，后续流程中迅速转移病人是重点。上面的提到的“早期目标治疗”或者“集束化治疗”，大家可以参考原文，在其protocol中要求的不是在急诊室完成，而是强调以上治疗应该在急诊室的开始，而后交接延续到ICU。目前急诊科成立监护室，改弦更张，自行全程治疗重症患者，将其短期医疗行为扩展延长到“长期医疗”的范畴是否合理，这在目前还很难说（至少我觉得并不合理与可行）。

急性有机磷农药中毒规范化诊断与救治

amicacin@gmail.com(Amic) — Tue,31 Jul 2007 18:22:11 +0800

急性有机磷农药中毒规范化诊断与救治
中南大学湘雅医院急诊科邓跃林

--------------------------------------------------------------------------------

急性有机磷农药中毒(AOPP)是一种非常凶险的急危重症,其毒性主要是抑制胆碱酯酶活性,使乙酰胆碱在体内过多蓄积,胆碱能神经受到持续冲动,导致先兴奋后衰竭的一系列毒蕈碱样、烟碱样和中枢神经系统症状,严重者出现昏迷和呼吸衰竭,甚至死亡。

据统计,我国农村和城镇有机磷农药中毒占急诊中毒的49.1%,居各种中毒之首。在中毒死亡患者中,因有机磷农药中毒致死者占83.6%。因此,怎样提高有机磷农药中毒抢救成功率,使死亡率降至最低,仍是我国急诊医学面临的艰巨任务。国外经验表明,推广急性有机磷农药中毒标准化及规范化治疗是降低死亡率的重要措施。固将急性有机磷农药中毒的规范化诊断方法和标准及主要解毒剂的规范统一使用做以下探讨,供同仁参考。

临床特征

有机磷农药中毒的临床表现包括急性胆碱能危象、中间型综合征、迟发性多发性神经病和局部损害四部分。

急性胆碱能危象

毒蕈碱样表现:恶心、呕吐、腹痛、腹泻、多汗、流涎、视力模糊、瞳孔缩小、呼吸困难、支气管分泌物增多,严重者出现肺水肿。

烟碱样表现:骨骼肌兴奋出现肌纤维震颤。常由小肌群开始,如眼脸、颜面、舌肌等,逐渐发展至肌肉跳动,牙关紧闭,颈项强直,全身抽搐等。

中枢神经系统表现:头痛、头昏、乏力、嗜睡、意识障碍、抽搐等。严重者出现脑水肿,或因呼吸衰竭而死亡。

中间型综合征

少数病例在急性中毒症状缓解后和迟发性神经病变发生之前(急性中毒后24~96小时)突然发生呼吸困难或死亡,称为“中间型综合征”。死亡前患者可先有颈、上肢和呼吸肌麻痹。累及脑神经者,可出现眼脸下垂眼外展障碍和面瘫。

迟发性多发性神经病

少数病例在急性中毒症状消失后2~3周可发生迟发性神经损害,出现感觉、运动型多发性神经病变表现,主要累及肢体末端,且可发生下肢瘫痪、四肢肌肉萎缩等。

局部损害

敌敌畏、敌百虫、对硫磷、内吸磷接触皮肤后可引起过敏性皮炎,并可出现水疱和剥脱性皮炎。有机磷杀虫药滴入眼中可引起结膜充血和瞳孔缩小。

诊断要点

1. 有有机磷接触史:发病前12h内的接触史有意义,超过1天以上无意义。

2. 有典型的中毒症状与体征:流涎、大汗、瞳孔缩小和肌颤(肉跳)。

3. 胆碱酯酶活力降低<70%。

临床分级

按照有机磷农药中毒的临床表现和胆碱酯酶活力指标,可将其分为轻、中、重三度。

轻度中毒:表现为头昏、头痛、恶心、呕吐、多汗、视物模糊、瞳孔缩小、胆碱酯酶活力为50%~70%;

中度中毒:除上述症状外,还有肌纤维颤动、瞳孔缩小明显、呼吸困难、流涎、腹痛,胆碱酯酶活力为50%~30%;

重度中毒:除上述症状外,还出现昏迷、肺水肿、呼吸麻痹、脑水肿,胆碱酯酶活力<30%。

在诊断中应特别注意与有机氮类农药(杀虫脒)中毒的鉴别,其鉴别要点见表1。

急性有机磷中毒的规范化治疗

急性有机磷中毒抢救原则包括:减少毒物吸收、促进体内毒物排泄和应用特效解毒药。现在此基础上对AOPP的规范化治疗提出建议。

1. 一般处理

立即脱离现场,至空气新鲜处。皮肤污染者,脱去衣物,立即用肥皂水或清水洗清(包括头发和指甲,最少2~3遍)。如发生眼污染,可用生理盐水或清水彻底冲洗。

催吐患者神志清楚且能合作时,让患者饮温水300~500 ml,然后自己用手指、压舌板或筷子刺激咽后壁或舌根诱发呕吐。如此反复进行,直至胃内容物完全吐出为止。患者处于昏迷、惊厥状态时不应催吐。催吐过程尽量使胃内容物排空,但需严防吸入气管致窒息,故需头侧位。

洗胃口服有机磷农药中毒患者要尽早接受彻底洗胃,一般在中毒后6h内,最好用洗胃机彻底清洗,在没有洗胃机的情况下,可从胃管注入300~500 ml清水,反复抽洗胃液,并尽快转送有洗胃机的医院。应特别注意洗胃需与阿托品、胆碱酯酶复能剂等治疗同时实施,紧急时可先用这些药物治疗后洗胃。

导泻目前主张洗胃后可从胃管注入硫酸钠20~40 g(溶于20 ml水)或注入20%甘露醇250 ml进行导泻治疗。这可抑制毒物吸收,促进毒物排泄。

2. 特效解毒药的应用

使用原则是“早期、足量、足疗程”。常用的药物有碘解磷定(PAM)和氯解磷定(PAM-CL)。

氯解磷定的应用国内推荐使用的肟类复能剂为氯解磷定,因其使用简单(肌肉注射)、安全、高效,可作为复能剂的首选(表2)。

碘解磷定的应用先静注碘解磷定负荷量1 g(稀释后静注,注射速度5~8分钟),必要时,1小时后重复上述用药1次,加入液体静滴,以0.25~0.5 g/h速度给药,维持有效血药浓度,总量不超过10 g/d。大多数患者持续用药4~6天,每天查血胆碱酯酶(ChE,试纸法),ChE活力稳定恢复至50%以上或临床症状消失,病情稳定好转时可逐渐减量或停药。一般减量时间为5~7天,每日减去半量,即5 g、2.5 g、1 g直至停药。

复能剂应用足量的指标当毒蕈碱样症状肌颤消失和胆碱酯酶活力为50%~60%时,可停药,如再次出现上述症状和指征,应该尽快补充用药,再次给予首次用药的半量。

合理的给药途径一般情况下以肌肉注射给药为宜。因为肌肉注射吸收较快,一般在3~5分钟即可出现疗效。另外,肌肉注射可使药物在血液中的半衰期比静脉注射给药长。

但当患者病情危重、注射部位血流缓慢或出现休克时,应采取静脉注射给药,但不宜静脉滴注给药。特别是首次给药应禁用静脉滴注给药,因为这样药物不能在短时内达到有效浓度。

3. 抗胆碱药的应用

阿托品阿托品的使用原则为:早期、适量、迅速达到“阿托品化”(表3)。有机磷农药毒性大,中毒症状发展快,生理拮抗剂(即抗胆碱能药)用药不及时可因支气管痉挛和分泌物堵塞支气管而致外周性呼吸衰竭,中毒剂量大时由于呼吸中枢抑制而致中枢性呼吸衰竭,这两者均可迅速导致死亡。因此,对于AOPP患者应迅速给予足量的外周抗胆碱能药物(如阿托品),以解除支气管痉挛和减少支气管分泌,但足量用药不等于过量用药。

阿托品足量的可靠指标为:口干、皮肤干燥和心率不低于正常值。毒蕈碱样症状消失(支气管痉挛解除和控制支气管分泌物过多)并出现“阿托品化”指征。过量的阿托品也可使神志改变,轻则躁动、谵妄,重者昏迷,因此不能以瞳孔大小、颜面潮红和神志变化作为达到“阿托品化”的必需指标,否则常导致阿托品严重过量,发生阿托品中毒或死亡。

长托宁长托宁使用方法见表4。

4. 含抗胆碱剂和复能剂的复方注射液

解磷注射液(每支含阿托品3 mg、苯那辛3 mg、氯磷定400 mg)起效快,作用时间较长。首次给药剂量:轻度中毒,1支,im,加用氯磷定0~0.5 g;中度中毒1~2支,im,加用氯磷定0.5~1.0 g;重度中毒2~3支,加用氯磷定1.0~1.5 g。用药后30~60 min可重复半量,以后视病情,可单独使用氯磷定和阿托品。

停药指标:主要中毒症状消失,胆碱酯酶活力达正常的50%~60%,可停药观察。停药12h以上,患者胆碱酯酶活力仍保持在60%以上时可考虑出院。

5. 对症治疗

AOPP患者主要死因是肺水肿、呼吸肌麻痹、呼吸中枢衰竭。另外,休克、急性脑水肿、中毒性心肌炎、心搏骤停等也是重要死因。因此,对症治疗应重点维持正常心肺功能,保持呼吸道通畅。出现呼吸衰竭时,应立即吸氧、吸痰,必要时行气管插管、人工呼吸。有肺水肿者,使用阿托品的同时可给予糖皮质激素、速尿。出现休克时,使用升压药。出现脑水肿时,使用脱水剂和糖皮质激素。按心律失常类型及时应用抗心律失常药物。这些治疗的同时维持水电解质、酸碱平衡,并给予保肝、抗生素等内科综合治疗。危重患者可输新鲜血浆治疗,以促进血中毒素排出及胆碱脂酶活力恢复。

6. 中间型综合征(IMS)的治疗

IMS多发生在重度中毒及早期胆碱酯酶复能剂用量不足的患者,及时行人工机械通气为抢救成功的关键。机械通气常规使用同步间歇性强制换气(SIMV)模式,帮助患者度过呼吸衰竭难关,同时也是提高患者抢救成功率,降低死亡率的重要救治措施。

7. 迟发性神经病变的治疗

除对症治疗外尚无特殊方法,其病程是一种良性经过。早期治疗可使用糖皮质激素(泼尼松30~60 mg,1w后逐渐减量),抑制免疫反应,缩短病程。其他药物包括营养神经药、大剂量B族维生素、三磷酸腺苷、谷氨酸、地巴唑、加兰他敏、胞二磷胆碱等。可配合理疗、体疗、针灸和按摩治疗,同时加强功能锻炼。另外,需使用阿托品及胆碱酯酶复能剂。

MEJM:恶性病引起的上腔静脉综合征(1)

amicacin@gmail.com(Amic) — Thu,17 May 2007 10:04:29 +0800

恶性病引起的上腔静脉综合征(1)

    一名58岁的男性因进行性劳力性呼吸困难、颈部肿胀、食欲减退和乏力2周就诊。患者没有晕厥或吞咽困难的病史。他已戒烟5年。体格检查显示患者心率105次／分，呼吸20次／分，颈部、胸部和上腹部的浅表血管扩张。无喘鸣音。应如何评估和处理本病例?
    临床问题   美国每年约有15,000例患者出现上腔静脉综合征，该综合征包括上腔静脉阻塞引起的一系列症状和体征。上半身静脉压升高导致头、颈和上肢水肿，经常伴有紫绀、多血质和皮下血管扩张(图1A)。水肿可引起喉或咽部功能障碍，表现为咳嗽、声音嘶哑、呼吸困难、喘鸣和吞咽困难。脑水肿可引起头痛、意识错乱和昏迷。静脉回流减少可导致血流动力学紊乱，这种并发症有可能是上腔静脉阻塞(内部或外部压迫)所致，也有可能是大的胸部肿物压迫心脏所致，或两种因素都存在。约三分之一患者在2周左右出现症状，其余患者在2周后出现症状。
    解剖和生理学
    上腔静咏将头部、上肢和躯干上部的血液运到心脏，所运血液约占静脉回心血的三分之一。纵隔中部或前纵隔的肿物(一般位于中线右侧)可压迫上腔静脉，例女口肿大的右侧气管旁淋巴结、淋巴瘤、胸腺瘤、炎性病变或主动脉瘤等。也可发生无外部压迫的上腔静脉血栓形成(图1B)。
    上腔静脉受阻时，血液通过侧支血管网流向下半身和下腔静脉或奇静脉。静脉侧支通常需要数周才能扩张到足够容纳上腔静脉血流的程度”。发生上腔静脉阻塞者的颈静脉压通常升高到20-40 mmHg(正常范围2-8 mmHg。症状的严重程度取决于上腔静脉狭窄的程度和狭窄的发生速度。
    上腔静脉阻塞引起的上半身水肿非常引入注目，但水肿的后果往往不太严重。
然而，罕见的脑水肿可能后果严重或可引起致命性后果。鼻部和喉头水肿可导致上呼吸道狭窄。上腔静脉阻塞引起的严重后果罕见。有人报告，在1986例发生上腔静脉阻塞的患者中，只有1例死亡。在有关发生神经或喉部功能受损的病例报告中，还不清楚是否存在其他致病因素如脑部转移瘤或气管压迫。

Figure 1. The Superior Vena Cava Syndrome.

Clinical findings in a patient with the superior vena cava syndrome, including facial edema, plethora, jugular venous distention, and prominent superficial vascularity of neck and upper chest, are shown in Panel A. The vascular anatomy of the upper chest, including the heart, superior vena cava, inferior vena cava, and subclavian vessels, is shown in Panel B. The tumor is shown compressing the superior vena cava.

    病因
    约在50年前，感染性疾病(尤其是梅毒性主动脉瘤和结核病)是绝大多数上腔静脉阻塞病例的病因。此后，这些病因越来越罕见，约在25年前，恶性病成为90％以上上腔静脉阻塞病例的病因。目前，血栓或非恶性疾病引起的上腔静脉阻塞约占总病例的35％，反映了血管内器械如导管和起搏器使用增多。最常见的恶性病因是非小细胞肺癌(约占50％的患者)、小细胞肺癌 (约占25％的患者)、淋巴瘤和转移性病变(每种约占10％的患者)。提示这些诊断的临床特点见表1。
    一般情况下，识别引起上腔静脉综合征的非恶性病因很简单，尤其是当此综合征与使用置入式血管内器械相关时。计算机体层摄影(CT)很容易识别主动脉瘤。诊断导致上腔静脉综合征的罕见病因——纤维性纵隔炎，需要进行活检。

策略和证据
    临床评估
    根据患者的体征和症状(表2)可以做出上腔静脉阻塞的临床诊断。采集病史时应注意症状的持续时间，既往的恶性病诊断，或既往接受血管内操作的情况。多数病例的症状在数周内进行性发展，某些病例随着侧支循环的建立，症状可能有所改善。症状的严重程度对确定是否需要进行紧急干预很重要。
影像学检查
最有用的影像学检查是注射造影剂后(评估上腔静脉的需要)的胸部CT。并发症不常见，包括静脉穿刺部位出血过多和造影剂过敏。通常仅在计划施行干预治疗(置入支架或手术)时，才进行静脉造影检查。对于不能耐受造影剂的患者，磁共振成像检查可能有用。正电子发射体层摄影(PET)有时也有用，因为它有可能影响放疗野的设计 (图2)。
    一般情况下，通过临床病史和CT影像检查结果，可以鉴别腔静脉血栓形成和外部压迫。必须要进行组织学诊断才能证实患者是否存在恶性病。就进行组织学诊断而言，在进行有创操作(如纵隔镜检查)之前，应通过临床评估来确定是否有合适的外周活检部位(例如一个可触及的锁骨上淋巴结)。通过痰的细胞学检查有可能对支气管内癌患者做出诊断。胸腔积液是常见现象(约三分之二上腔静脉综合征患者有此体征)，强烈建议医师考虑胸腔穿刺术和细胞学分析，因为这些检查简单易行，尽管其对这类患者的诊断率只有大约 50％。支气管镜检查的诊断率为50％- 70％，经胸针吸活检的诊断率约为 75％，而纵隔镜检查或纵隔切开术的诊断率超过90％。尤其是对于淋巴瘤病例，需要取得足够的组织，才能明确其结节的结构特征和细胞类型特征，还需要通过免疫组化检查来证实其亚型。
    尽管某些研究提示，上腔静脉综合征患者接受纵隔操作时的并发症发生率高于没有该综合征的患者，但其他研究报告，即使存在上腔静脉综合征时并发症的发生率也很低。一项纳入 319例上腔静脉综合征患者的回顾性研究发现，3％接受纵隔镜检查或纵隔切开术的患者发生大出血(没有特别定义)。支气管镜检查(纤维光学镜和硬式镜)与(并发症的)危险较低(发生出血的危险为0．5％，发生呼吸窘迫的危险为0．5％)相关。

    处理
    与恶性病相关的上腔静脉综合征的治疗，包括治疗癌症和缓解阻塞的症状。多数有关治疗上腔静脉综合征的资料来自病例系列研究，随机临床试验稀少。发生上腔静脉阻塞患者的中位寿命约为6个月，但由于基础恶性病不同，这一估计值有很大变异。有与恶性病相关的上腔静脉阻塞表现的患者，其生存率似乎与未发生上腔静脉阻塞、但患有相同类型的肿瘤和处于相同疾病阶段的患者的生存率没有显著差异。在某些患者中，治疗上腔静脉综合征及其恶性病可同时缓解两种疾病。
    应根据患者症状和基础恶性病的严重程度，以及预计患者对治疗的反应来设计处理方案例如，淋巴瘤、小细胞肺癌或生殖细胞瘤患者对单纯全身化疗的临床疗效反应通常很迅速。在大多数非小细胞肺癌患者中，抗癌治疗(对Ⅳ期肺癌患者进行化疗，对Ⅲ期肺癌患者进行化疗加放疗)可减轻上腔静脉阻塞的症状，但患者的反应程度和速度不如淋巴瘤、小细胞肺癌或生殖细胞瘤患者。

支持性治疗和药物治疗
一种显而易见的治疗策略是抬高患者的头部以降低静水压，从而减轻水肿。没有资料证实这种策略的有效性，但此法简单，没有危险。医师经常给患者使用糖皮质激素治疗(地塞米松 4mg，每6小时1次)，尽管尚未对其疗效进行很好的正式研究，而且只有病例报告提示这种疗法有益。糖皮质激素可减少淋巴瘤和胸腺瘤的肿瘤负荷，因此，与其他类型的肿瘤患者相比，糖皮质激素更易于减轻淋巴瘤或胸腺瘤患者的阻塞症状。袢利尿剂也是常用药物，但是还不明确阻塞部位远端的静脉压是否会受右心房压力轻度改变的影响。一项观察性研究纳入107例由各种原因引起的上腔静脉综合征患者，临床改善率(总改善率为 84％)在接受糖皮质激素、利尿剂治疗或两者都不用的患者中相似。
    在发生了与置人导管相关的血管内血栓，并因此引起上腔静脉阻塞的患者中，应当考虑去除导管。在去除导管的同时应进行抗凝治疗(见不确定领域节)。
放疗
放疗经常用于治疗有恶性病导致的上腔静脉阻塞症状的患者，使用前需要进行组织诊断。大多数引起上腔静脉综合征的肿瘤类型对放疗敏感。一项系统回顾分析发现，治疗2周时，78％的小细胞肺癌患者和63％的非小细胞肺癌患者的上腔静脉阻塞症状完全缓解。症状在72小时内经常有明显改善。
    然而，腔静脉阻塞变化的客观测定值与患者报告的症状改善程度不平行。一项有关接受放疗患者的病例系列研究(放疗是其中多数患者的唯一治疗)显示，用系列静脉造影片测量腔静脉的阻塞情况，31％患者的阻塞完全消除，23％患者的阻塞部分消除。在尸检研究中，仅14％患者的(腔静脉)完全通畅，10％患者的(腔静脉)部分通畅，尽管85％的患者报告其症状缓解。这些研究结果提示，侧支循环的建立可能有助于改善患者的症状。在对化疗敏感的肿瘤患者中，在开始化疗前紧急启动放疗的价值不确定，上述结果进一步强调了这种不确定性。
    如果将放疗作为初始治疗，放射野应包括整个病变和邻近的淋巴结区域，应考虑到肺和心脏组织的容积，将并发症减至最少。对大多数淋巴瘤患者，建议使用基于CT的模拟定位技术(用于设计放疗野)和每日分割照射量为1.8~2.0 Gy的放疗。无论是在治疗之初，还是在初次短程放疗之后，都应根据包括全身化疗在内的多学科治疗计划制定总放射剂量。治疗小细胞和非小细胞肺癌经常使用相同的初次放疗疗程，每日分割照射量较高，为2.0~3.0Gy。在施行几次分割照射后，随着患者的症状开始减轻和医师着手为患者制定后续治疗方案，有可能改变放射野的大小和构形。当以放疗作为姑息治疗时，一般情况下的疗程为1~3周，采用每日分割照射的方法进行。

Figure 2. Chest Radiograph and PET–CT Scans of a Patient with the Superior Vena Cava Syndrome.

Panel A shows a chest radiograph of a patient with the superior vena cava syndrome caused by small-cell lung cancer. Panel B shows a PET–CT scan (CT without contrast) of the same patient. Panel C shows a PET–CT scan (CT without contrast) after the patient had undergone 5 weeks of systemic chemotherapy. The arrow identifies the superior vena cava — an identification that is challenging without contrast enhancement.

（Volume 356:1862-1869 nejm）

黄教授专栏：本周危重病文献信息（2）

amicacin@gmail.com(Amic) — Tue,08 May 2007 16:44:37 +0800

本周肺栓塞文献荟萃（2）

37: Lancet. 2007 Apr 21;369(9570):1347-55.
Comment in: Lancet. 2007 Apr 28;369(9571):1413-5.
The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison.
Sherman DG, Albers GW, Bladin C, Fieschi C, Gabbai AA, Kase CS, O'Riordan W, Pineo GF; PREVAIL Investigators.
Department of Medicine (Neurology), University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. sherman@uthscsa.edu
BACKGROUND: Venous thromboembolism prophylaxis with low molecular weight heparin or unfractionated heparin is recommended in acute ischaemic stroke, but which regimen provides optimum treatment is uncertain. We aimed to compare the efficacy and safety of enoxaparin with that of unfractionated heparin for patients with stroke. METHODS: 1762 patients with acute ischaemic stroke who were unable to walk unassisted were randomly assigned within 48 h of symptoms to receive either enoxaparin 40 mg subcutaneously once daily or unfractionated heparin 5000 U subcutaneously every 12 h for 10 days (range 6-14). Patients were stratified by National Institutes of Health Stroke Scale (NIHSS) score (severe stroke > or =14, less severe stroke <14). The primary efficacy endpoint was the composite of symptomatic or asymptomatic deep vein thrombosis, symptomatic pulmonary embolism, or fatal pulmonary embolism. Primary safety endpoints were symptomatic intracranial haemorrhage, major extracranial haemorrhage, and all-cause mortality. This study is registered with ClinicalTrials.gov, number NCT00077805. FINDINGS: In the efficacy population (ie, one or more dose received, presence of deep vein thrombosis or pulmonary embolism, or assessment for venous thromboembolism), enoxaparin (n=666) and unfractionated heparin (669) were given for 10.5 days (SD 3.2). Enoxaparin reduced the risk of venous thromboembolism by 43% compared with unfractionated heparin (68 [10%] vs 121 [18%]; relative risk 0.57, 95% CI 0.44-0.76, p=0.0001; difference -7.9%, -11.6 to -4.2); this reduction was consistent for patients with an NIHSS score of 14 or more (26 [16%] vs 52 [30%]; p=0.0036) or less than 14 (42 [8%] vs 69 [14%]; p=0.0044). The occurrence of any bleeding was similar with enoxaparin (69 [8%]) or unfractionated heparin (71 [8%]; p=0.83). The frequency of the composite of symptomatic intracranial and major extracranial haemorrhage was small and closely similar between groups (enoxaparin 11 [1%] vs unfractionated heparin 6 [1%]; p=0.23). We noted no difference for symptomatic intracranial haemorrhage between groups (4 [1%] vs 6 [1%], respectively; p=0.55); the rate of major extracranial bleeding was higher with enoxaparin than with unfractionated heparin (7 [1%] vs 0; p=0.015). INTERPRETATION: Our results suggest that for patients with acute ischaemic stroke, enoxaparin is preferable to unfractionated heparin for venous thromboembolism prophylaxis in view of its better clinical benefits to risk ratio and convenience of once daily administration.关于LWMH的又一篇**文章，而且肯定会在之后的所谓指南中内引用提及。首先为什么开标就是一个很值得研究的问题，多数开标研究就是为了避免实验药物不明原因或不可预测的副作用，或者由于出现未能预测到的严重并发症而被迫开标，结论中也证实严重的颅内大出血在LWMH组中显著增加，但是作者还是恬不知耻的用“We noted no difference for symptomatic intracranial haemorrhage between groups ”，我真的搞不懂为什么要如此表述。最近关于活性蛋白C的一个在儿科应用的临床研究就由于小儿中发生颅内出血过高（活性蛋白C组大概2-4例，对照组1例）而提前终止。我们现在回过头看看这个LWMH，同样是颅内出血的高发生率却仍然能够理直气壮的推荐，难道老人和小孩的生命是不平等吗？我可以毫不掩饰地说，尽管有越来越多的数据“提示”了LWMH的多数未经统计学证实的所谓的优越性，但却越来越真实地证明了普通肝素的应用价值和低并发症，尤其是致死性并发症的低发生率。因此对于普通肝素的应用价值一定要放到首选的高度，让LWMH见鬼去吧—— 一支普通肝素（12500单位/支）人民币大概4元，可以用两次皮下注射，一支LWMH大概70元/支，一天至少两只，性价比不言自明。

44: Cochrane Database Syst Rev. 2007 Apr 18;(2):CD006466.
Oral anticoagulation for prolonging survival in patients with cancer.
Akl E, Kamath G, Kim S, < a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Yosuico+V%22%5BAuthor%5D">Yosuico V, Barba M, Terrenato I, Sperati F, Schunemann H.
BACKGROUND: A number of basic research and clinical studies have led to the hypothesis that oral anticoagulants may improve the survival of patient s with cancer through an antitumour effect in addition to their antithrombotic effect. OBJECTIVES: To evaluate the effectiveness and safety of oral anticoagulation (including vitamin K antagonists and ximelagatran) as an intervention to improve survival of patients with cancer. SEARCH STRATEGY: A comprehensive search for studies of anticoagulation in cancer patients including (1) a January 2007 electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ISI the Web of Science; (2) hand search of the American Society of Clinical Oncology (starting with its first volume, 1982) and of the American Society of Hematology (starting with its 2003 issue); (3) checking of references of included studies; and (4) use of "related article" feature in PubMed. SelectION CRITERIA: Randomized clinical trials (RCTs) comparing vitamin K antagonist or ximelagatran to no intervention or placebo in cancer patients without clinical evidence of venous thromboembolism. DATA COLLECTION AND ANALYSIS: Using a standardized data form we extracted data on methodological quality, participants, interventions and outcome of interest that included all cause mortality, symptomatic deep venous thrombosis, symptomatic pulmonary embolism, major bleeding and minor bleeding. MAIN RESULTS: Of 3986 identified citations five RCTs fulfilled the inclusion criteria. Warfarin was the oral anticoagulant in all of these RCTs and it was compared to either placebo or no intervention. The overall methodological quality of these RCTs was acceptable. The effect of warfarin on reduction in mortality was not statistically significant at six months (Relative risk (RR) = 0.96; 95% CI 0.80 to 1.16), at one year (RR = 0.95; 95% CI 0.86 to 1.05) at 2 years (RR = 0.97; 95% CI 0.87 to 1.08) or at five years (RR 0.91; 95% CI 0.83 to 1.01). In the subgroup of patients with small cell lung cancer (SCLC), warfarin reduced mortality at six months (RR = 0.69; 95% CI 0.50 to 0.96) but not at one year (RR = 0.88; 95% CI 0.77 to 1.01). This six month mortality benefit was statistically significant in the subgroup of extensive SCLC (RR = 0.65; 95% CI 0.45 to 0.93) but not in the subgroup of limited SCLC (RR = 0.68; 95% CI 0.36 to 1.28). One study assessed the effect of warfarin on venous thromboembolism and showed a RR reduction of 85% (p = 0.031). Warfarin increased both major bleeding (RR = 4.24; 95% CI 1.85 to 9.68) and minor bleeding (RR = 3.34; 95% CI 1.66 to 6.74). Warfarin increased the risk of major bleeding (RR 5.46; 95% CI 3.04 to 9.81) and minor bleeding (RR 4.01; 95% CI 1.30 to 12.42) also in patients with SCLC. There was no evidence for a significant reduction in mortality in any other cancer subtype. AUTHORS' CONCLUSIONS: Existing evidence does not suggest a mortality benefit from oral anticoagulation in patients with cancer. In patients with SCLC, the evidence suggests a survival benefit at six months from warfarin particularly when the disease is extensive. The decision for a patient with extensive SCLC to start warfarin for survival benefit should balance that benefit with the downsides of increased bleeding risk in light of patient values for these outcomes.

45: Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005259.
Interventions for preventing venous thromboembolism in adults undergoing knee athroscopy.
Ramos J, Perrotta C, Badariotti G, Berenstein G.
BACKGROUND: Knee arthroscopy is a frequent surgical procedure. Arthroscopy procedures are considered minimally invasive. However, some patients will need extended surgical time, suffer injury and immobilization thus increasing the risk for thromboembolic events. Incidence of deep venous thrombosis (DVT) in patients undergoing knee arthroscopy is reported to be from 0.6% to 17.9% depending on the diagnostic method used. Different approaches are available for thromboprophylaxis (mechanical or pharmacological). OBJECTIVES: To assess the effectiveness and safety of thromboprophylaxis to reduce the incidence of DVT in patients undergoing knee arthroscopy. SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular Diseases Group Specialized Register (last searched October 2006) the CENTRAL (last searched Issue 4, 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), and Lilacs (1988 to 2006). We contacted specialists known to be involved in phlebology and interested in post thrombotic syndrome for details of unpublished and ongoing trials. SelectION CRITERIA: Randomized clinical trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not (i.e. double blinded, single blinded or unblinded) of all type of interventions, whether mechanical or pharmacological, single or in combination, used to prevent DVT in males and females over 18 years old undergoing knee arthroscopy. There was no restriction on language. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Four trials involving 527 predominantly male participants were included. The main weakness of the studies was the lack of correct stratification of the arthroscopic intervention.The relative risk (RR) of thrombotic events was 0.20 (95% confidence interval (CI); 0.07 to 0.57) comparing any type of low molecular weight heparin (LMWH) versus placebo. All thrombotic events but one (pulmonary embolism in the LMWH group) were distal venous thrombosis. Adverse events were most common in the intervention group than in the control group, RR 2.11 (95% CI 1.26 to 3.55). There were 66 episodes of adverse events. The number needed to harm was 20 for any adverse events. AUTHORS' CONCLUSIONS: This meta-analysis suggests that LMWH reduces the incidence of distal DVT diagnosed by sonogram. The clinical benefit of this is uncertain. No strong evidence was found to conclude thromboprophylaxis is effective to prevent thromboembolic events and safe, in people with unknown risk factors for thrombosis, undergoing knee arthroscopy.以上两篇荟萃分析可以一看，有的时候我总是想这些荟萃分析的真实动机是什么，如果癌症患者接受了抗凝药物，它的预后就会好转吗，因抗凝导致的并发症会不会加速癌症病人的死亡，谁最终将从抗凝治疗中获益....

49: Br J Surg. 2007 Apr 17; [Epub ahead of print]
High preoperative prevalence of deep venous thrombosis in patients with colorectal cancer.
Stender MT, Nielsen TS, Frokjaer JB, Larsen TB, Lundbye-Christensen S, Thorlacius-Ussing O.
Department of Surgical Gastroenterology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
BACKGROUND:: Deep venous thrombosis (DVT) is a major complication of cancer and a predictor of reduced survival. The postoperative prevalence of DVT in colorectal cancer surgery is high, but the preoperative prevalence is unknown. The aim of this observational study was to estimate the preoperative prevalence of DVT in patients with colorectal cancer. METHODS:: Some 193 consecutive patients with newly diagnosed colorectal cancer admitted for intended curative surgery were examined with compression ultrasonography for DVT before surgery. RESULTS:: DVT was detected in 15 (7.8 per cent) of the 193 patients, with a prevalence of 16 per cent in women (12 of 76) versus 2.6 per cent in men (three of 117 (adjusted odds ratio (OR) 5.8 (95 per cent confidence interval (c.i.) 1.4 to 23.2)). The risk of DVT was strongly correlated with increasing American Society of Anesthesiologists (ASA) risk score: adjusted or 6.8 (95 per cent c.i. 1.6 to 28.7 for ASA group III or IV versus ASA group I or II). Pulmonary embolism was detected in two patients (1.0 per cent). CONCLUSION:: A high preoperative prevalence of DVT was observed in patients with colorectal cancer, especially among women and patients in ASA groups III and IV. Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

52: Ann Hematol. 2007 Apr 17; [Epub ahead of print]
Suboptimal doses of low molecular weight heparin and acute venous thromboembolism. Data from the RIETE registry.
Bruscas MJ, Nieto JA, Perez-Pinar M, Lopez-Jimenez L, Fernandez-Capitan C, Lopez-Chulia F, orue-Lecue MT; for the RIETE Investigators.
Servicio de Medicina Interna, Hospital Virgen de la Luz, 16002, Cuenca, Spain, joseanietor@terra.es.
The objective was to assess the use of suboptimal doses (60-149 UI kg(-1) day(-1)) of low molecular weight heparin (LMWH) in the treatment of acute venous thromboembolism (VTE) in actual clinical practice and to evaluate the outcomes compared to standard doses (>/=150 UI kg(-1) day(-1)). Retrospective analysis of data from a multicenter registry of patients with VTE (RIETE; Registro Informatizado de Enfermedad TromboEmbolica). Patient characteristics, antithrombotic treatments, and 3-month outcomes were analyzed. We studied 12,302 patients with VTE; 10,524 patients were treated initially only with LMWH; 1,547 patients received suboptimal LMWH (mean = 122 UI kg(-1) day(-1)), and 8,977 patients received full-dose LMWH (mean = 191 UI kg(-1) day(-1)). The suboptimal group included significantly more patients with recent major bleeding, weight more than 100 kg, raised creatinine, or deep vein thrombosis. No significant differences in mortality rate (7.7 vs 7.8%), VTE recurrence (2.7 vs 2.3%), or fatal hemorrhage (0.6 vs 0.6%) occurred between the suboptimal and the standard group. Major bleeding episodes occurred more frequently in the patients with pulmonary embolism treated with suboptimal LMWH (4.5 vs 2.4%; p = 0.02). In the multivariate analysis, after adjusting for bleeding risk factors, major hemorrhage was not associated with the heparin dose. Suboptimal doses of LMWH are used in actual clinical practice in a reduced group of patients at an outcome rate not very different to that of standard doses. Bleeding episodes depend more on the patient's characteristics than on the LMWH dose. Randomized trials should be performed to corroborate these results.

55: Semin Hematol. 2007 Apr;44(2):62-9.
Epidemiology and risk factors for venous thrombosis.
Cushman M.
Department of Medicine, Thrombosis and Hemostasis Program, University of Vermont College of Medicine and Fletcher Allen Health Care, Burlington, VT, USA. mary.cushman@uvm.edu
Venous thrombosis, including deep vein thrombosis (DVT) and pulmonary embolism (PE), occurs at an annual incidence of about 1 per 1,000 adults. Rates increase sharply after about age 45 years, and are slightly higher in men than women in older age. Major risk factors for thrombosis, other than age, include exogenous factors such as surgery, hospitalization, immobility, trauma, pregnancy, and the puerperium and hormone use, and endogenous factors such as cancer, obesity, and inherited and acquired disorders of hypercoagulation. This review focuses on epidemiology of venous thrombosis and the general implications of this in patient management.

62: Acta Haematol. 2007 Apr 10;118(1):10-18 [Epub ahead of print]Upper Limb Deep Vein Thrombosis: A Literature Review to Streamline the Protocol for Management.
Sajid MS, Ahmed N, Desai M, Baker D, Hamilton G.
Department of Vascular Surgery, Royal Free Hospital, Hampstead, London, UK.
Objective: The objective of this article is to provide up-to-date information about aetiology, pathogenesis, diagnostic modalities and treatment of upper limb deep vein thrombosis (ULDVT).关于上肢深静脉血栓的综述 Methods: Generic terms including ULDVT, axillary-subclavian DVT, and complications of central venous catheters were searched on electronic database. We analysed original studies, review articles and evaluation studies published over the last 25 years. Results: Forty-seven studies on ULDVT encompassing 2,557 patients were evaluated. The incidence of ULDVT was quoted 1-4% of the total DVT. Primary ULDVT (20% of the total) was due to activity-related venous trauma. Secondary ULDVT (80% of the total) was due to central venous catheters and malignancy. Duplex ultrasound (sensitivity 78-100% and specificity 82-100%), contrast venography (gold standard) and magnetic resonance venography were the diagnostic tools used. Pulmonary embolism (2-35%) and post-thrombotic syndrome (7-46%) were the main sequelae. Anticoagulation was the universal intervention, giving 79% symptom relief (13.2% rethrombosis rate). Thrombolysis and/or percutaneous thrombectomy were used in 38% of cases for the management of ULDVT, giving 83% symptom relief (90% recanalization rate and 9% rethrombosis rate). Surgical decompression, venous angioplasty and superior vena cava filters were the main adjunctive interventions. Conclusion: ULDVT, although rare, is associated with considerable morbidity and mortality (29-40%) due to potential risks of pulmonary embolism, post-thrombotic syndrome and loss of vascular access. Simple anticoagulation is suitable for the majority of patients. Thrombolysis/thrombectomy is often successful but less frequently used. Surgical decompression, venous angioplasty and superior vena cava filters have some role in recurrent cases. An optimal management protocol can be established using a multimodality approach.

63: Catheter Cardiovasc Interv. 2007 Apr 9; [Epub ahead of print]Percutaneous rheolytic thrombectomy for large pulmonary embolism: A promising treatment option.
Chauhan MS, Kawamura A.
Department of Cardiovascular Medicine, Lahey Clinic Medical Center, Burlington, Massachusetts.
Background: Pulmon ary embolism (PE) is a common cardiovascular disease with significant mortality. Some patients with large PE are not eligible for current treatment options such as thrombolysis or surgical embolectomy. We report our experience of percutaneous rheolytic thrombectomy (PRT) using the AngioJet system combined with adjunctive local thrombolytic therapy and inferior vena cava (IVC) filter placement to treat massive or submassive PE in patients ineligible for current treatment options. Methods and Results: Of the 14 consecutive patients ineligible for thrombolysis or embolectomy treated with PRT, 10 patients had massive PE (6 patients were hypotensive and 4 patients had intractable hypoxemia) and 4 patients had submassive PE. Adjunctive local thrombolysis was performed in 5 patients. An IVC filter was placed in 11 patients. Angiographic success based on Miller score was achieved in 13 patients (92.9%). Procedure success was obtained in 12 patients (85.7%). Procedural mortality occurred in one patient who presented in cardiogenic shock (7.1%) and non-fatal hemoptysis occurred in 1 patient (7.1%). Total in-hospital mortality occurred in 3 patients (21.4%). On a mean follow-up of 9 months, all 11 survivors had noted significant improvement in symptoms without recurrence. Conclusions: Percutaneous rheolytic thrombectomy using the AngioJet may be a treatment option for patients with massive or submassive PE who may not be eligible for thrombolytic therapy or surgical embolectomy. 关于介入治疗急性大块肺栓塞的报道已不鲜见。如果将1970年greenfield开始应用下腔静脉滤器作为肺栓塞介入治疗元年的话，近30年来，无论是腔静脉滤器还是肺血管内的介入治疗都已经今非昔比了。粗略的统计，仅肺动脉内介入治疗方法学的报道已经不下百例，但可能由于设备，人员以及实验设计，伦理学等问题，目前急性大块肺栓塞的介入治疗与其他诸如溶栓、外科治疗的比较研究还是非常稀缺的，多数研究都是如上的观察性研究。就如同MRI之于肺栓塞的诊断，介入治疗之于溶栓治疗，即生喻何生亮的感觉！MRI的普及指日可待，介入治疗则恐怕永远只能处于次席了。

70: J Trauma. 2007 Mar;62(3):570-6.Extracorporeal life support for massive pulmonary embolism.
Maggio P, Hemmila M, Haft J, Bartlett R.
Department of Surgery, University of Michigan Medical Center, MI 48109, USA. pmaggio@umich.edu
BACKGROUND: Massive pulmonary embolism is frequently lethal because of acute irreversible pulmonary and cardiac failure. Extracorporeal life support (ECLS) has been used for cardiopulmonary failure in our institution since 1988, and we reviewed our experience with its use in the management of massive pulmonary emboli. METHODS: We reviewed our complete experience with ECLS for massive pulmonary emboli from January 1992 through December 2005. The records of 21 patients were examined and data extracted. RESULTS: During the study period, 21 patients received ECLS for massive pulmonary emboli. All patients were on vasoactive drugs, acidemic, and hypoxic at the time of institution of ECLS. Eight were in active cardiac arrest. Five were trauma patients, eight had recently undergone an operation, and six had a hypercoagulable disorder. Nineteen of the 21 patients were cannulated for venoarterial bypass and two were placed on venovenous bypass. The average duration of support for survivors was 5.4 days, ranging from 5 hours to 12.5 days. Emboli resolved with anticoagulation in 10 of 13 survivors and 4 of 13 survivors underwent surgical pulmonary embolectomy. Catastrophic neurologic events were the most common cause of mortality in our series; four patients died from intracranial hemorrhage. The overall survival rate was 62% (13/21). CONCLUSIONS: We conclude that emergent ECLS provides an opportunity to improve the prognosis of an otherwise near-fatal condition, and should be considered in the algorithm for management of a massive pulmonary embolism in an unstable patient. 还是美国厉害，你看不稳定的急性肺栓塞高级声明支持已经用上了膜肺，为后续的对症治疗提供了时机，羡慕中...

73: J Cardiovasc Med (Hagerstown). 2007 Apr;8(4):253-7.
Pulmonary embolism and deep venous thrombosis in hospitalized adults with chronic obstructive pulmonary disease.
Stein PD, Beemath A, Meyers FA, Olson RE.
St Joseph Mercy Oakland Hospital, Pontiac 48341-5023, and Wayne State University, Detroit, Michigan, USA. steinp@trinity-health.org
BACKGROUND: Hospitalized patients with exacerbations of chronic obstructive pulmonary disease (COPD), when routinely evaluated for pulmonary embolism (PE), show PE in 25-29% of cases. We assessed the rate of diagnosis of PE and deep venous thrombosis (DVT) in hospitalized patients with COPD and the influence of age on relative risk compared with hospitalized patients who do not have COPD. METHODS: A retrospective evaluation of data in hospitalized adults with and without COPD from the National Hospital Discharge Survey. RESULTS: From 1979 to 2003, 58,392,000 adults 20 years of age and older, were hospitalized with COPD in the United States. Among these patients, PE was diagnosed in 381,000 (0.65%) and DVT in 632,000 (1.08%). The relative risk of PE in adults hospitalized with COPD was 1.92 and for DVT it was 1.30. Relative risks were age dependent. Among those aged 20-39 years with COPD, the relative risk of PE was 5.34. Among patients aged 40-59 years, the relative risk of PE decreased to 2.02, and among patients aged 60-79 years the relative risk of PE was 1.23. CONCLUSION: These data, when compared with the rate of diagnosis of PE in hospitalized patients with exacerbations of COPD, all of whom were evaluated for PE, indicate that PE in patients with COPD is generally underdiagnosed. In young adults, other risk factors in combination with COPD are uncommon, so the contribution of COPD to the risk of PE becomes more apparent than in older patients.

76: N Engl J Med. 2007 Apr 5;356(14):1438-44.
Clinical practice. Prophylaxis for thromboembolism in hospitalized medical patients.
Francis CW.
Department of Hematology and Oncology, University of Rochester Medical Center, Rochester, NY 14642, USA. charles_francis@urmc.rochester.edu 新英格兰医学的综述还是要收藏的。

77: J Am Coll Cardiol. 2007 Mar 27;49(12):1334-9. Epub 2007 Mar 9.
Abnormal left ventricular diastolic filling in chronic thromboembolic pulmonary hypertension: true diastolic dysfunction or left ventricular underfilling?
Gurudevan SV, Malouf PJ, Auger WR, Waltman TJ, Madani M, Raisinghani AB, DeMaria AN, Blanchard DG.
Division of Cardiolo gy, University of California Irvine School of Medicine, Irvine, California, USA.
OBJECTIVES: The purpose of this study was to investigate the cause of abnormal left ventricular (LV) Doppler diastolic filling characteristics in chronic thromboembolic pulmonary hypertension (CTEPH). BACKGROUND: In CTEPH, LV diastolic function often appears abnormal. It is unclear whether this "impaired relaxation" (EThe results of this study strongly suggest that the impaired relaxation pattern observed in patients with CTEPH is not solely the result of geometric effects of RV enlargement and LV chamber distortion but is caused in large part by low LV preload and relative underfilling.

82: J Thromb Haemost. 2007 Mar;5(3):483-9.
Treprostinil for severe inoperable chronic thromboembolic pulmonary hypertension.
Skoro-Sajer N, Bonderman D, Wiesbauer F, Harja E, Jakowitsch J, Klepetko W, Kneussl MP, Lang IM.
Division of Cardiology, Vienna General Hospital, Medical University of Vienna, Vienna , Austria. nika.skoro-sajer@meduniwien.ac.at
BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) results from non-resolving pulmonary thromboemboli that are resistant to plasmatic anticoagulation. Because of a secondary pulmonary arteriopathy accompanying major vessel obstruction, the disorder may be a target for vasodilator therapy. OBJECTIVES: In an open-label uncontrolled study, we investigated the prostacyclin analog treprostinil given s.c. in patients with severe inoperable CTEPH. METHODS: Between September 1999 and September 2005, 25 patients were included if their World Health organization (WHO) functional class was III or IV, if their six-minute walking distance (6-MWD) Treprostinil improves exercise capacity, hemodynamics and survival in patients with severe inoperable CTEPH. We speculate that the effects may be explained by a combined vasodilatory, platelet-antagonistic and potential antiproliferative action of the drug.

86: Respir Med. 2007 Mar;101(3):389-98. Epub 2007 Jan 11.
Diagnosis and management of pulmonary hypertension over the past 100 years.
van Wolferen SA, Grunberg K, Vonk Noordegraaf A.
Department of Pulmonary Diseases, Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Pulmonary hypertension is a rare disease with a poor prognosis. It was first described in the late 19th century as a clinical-pathological syndrome characterised by obstruction of the small pulmonary arteries and right ventricular hypertrophy in patients presenting with severe dyspnoea and cyanosis. After the development of right heart catheterisation in the second half of the 20th century, it was found that many diseases could cause pulmonary hypertension, which is now recognised to be high blood pressure in the arteries that supply the lungs. In the 1960s, an epidemic of pulmonary hypertension caused by appetite suppressants initiated a systematic collection of information on pulmonary hypertension, leading to the first international classification of pulmonary hypertension. Increased understanding of the pathogenesis of the various forms of pulmonary hypertension has led to novel treatments and holds promise for the future. 看题目就知道是一篇关于肺动脉高压百年治疗的历史性综述，收藏！

黄教授专栏：本周危重病文献信息（1）

amicacin@gmail.com(Amic) — Tue,08 May 2007 16:42:25 +0800

本周肺栓塞文献荟萃(1)

利用Pubmed的订阅功能可以按照自己的需要定时获得专业领域或者个人研究方向的最新出版信息，我目前订的有大约3-4个主题，比如Sepsis，ARDS和肺栓塞等。奇怪的是最近一直没有收到肺栓塞的更新。今天终于收到，条目大约有102篇，可笑的是这次连2004年《中华结核和呼吸杂志》的出版内容都有，部分还有其他国外杂志2006年的陈旧信息，不知道Pubmed怎么搞的。好了，闲话少说，看看这次关于VTE/PTE/DVT有什么新的消息或者进展吧（我已经剔除了部分条目，留下个人认为最主要的内容，重点地方用红色标出）:

2: J Nucl Med. 2007 May;48(5):680-684.
Ventilation-Perfusion Scintigraphy Is More Sensitive than Multidetector CTPA in Detecting Chronic Thromboembolic Pulmonary Disease as a Treatable Cause of Pulmonary Hypertension.
Tunariu N, Gibbs SJ, Win Z, Gin-Sing W, Graham A, Gishen P, Al-Nahhas A.
Department of Radiology, Hammersmith Hospital, London, United Kingdom; 2Department of Cardiology, Hammersmith Hospital, London, United Kingdom; 3Imperial College, London, United Kingdom; and 4Department of Nuclear Medicine, Hammersmith Hospital, London, United Kingdom.
Pulmonary hypertension (PH) is a progressive disease with a poor prognosis. Identifying chronic thromboembolic pulmonary disease as a cause of PH has major clinical implications as these patients could be potentially offered a surgical cure. Ventilation-perfusion (V/Q) scintigraphy has a high sensitivity to detect embolic disease but its value has been challenged with the emergence of multidetector CT pulmonary angiography (CTPA). We compared the value of V/Q scintigraphy with CTPA in detecting chronic thromboembolic pulmonary disease. METHODS: We retrospectively reviewed the results of V/Q scintigraphy and CTPA performed on patients who had been referred to the Pulmonary Hypertension Service at Hammersmith Hospital between 2000 and 2005. A total of 227 patients (85 males, 142 females; age range, 18-81 y; mean age, 42 y) had all tests done at Hammersmith Hospital and were included in the study. Interpretation of scans was according to the modified PIOPED (Prospective Investigation of Pulmonary Embolism Diagnosis) criteria. CTPA was considered as suggestive of chronic thromboembolic pulmonary disease if it showed visualization of the thrombus or webs, recanalization, perfusion abnormalities, stenosis, or strictures. Standard pulmonary angiography was performed via femoral approach. In 90% of the cases, CTPA and V/Q scintigraphy were performed within 10 d. RESULTS: Seventy-eight patients (group A) had a final diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) and 149 (group B) had non-CTEPH etiology. Among group A, V/Q scintigraphy was reported as high probability in 75 patients, intermediate probability in 1 patient, and low probability in 2 patients. CTPA was positive in 40 patients and negative in 38 patients. Among group B, V/Q scintigraphy was reported as low probability in 134, intermediate probability in 7, and high probability in 8 patients. CTPA was negative in 148 patients and false-positive in 1 patient. Statistical analysis showed V/Q scintigraphy to have a sensitivity of 96%-97.4% and a specificity of 90%-95%. CTPA showed a sensitivity of 51% and a specificity of 99%. CONCLUSION: Our results demonstrate that V/Q scintigraphy has a higher sensitivity than CTPA in detecting CTEPH as a potential curable cause of PH. 总结：本文大概是不多的几篇能够证实通气/灌注扫描的敏感性优于多层螺旋CT的文章—— 对于因慢性血栓性栓子导致的肺动脉高压，通气灌注扫描的敏感性96~97.4%，多层螺旋CT造影的敏感性仅51%，特异性方面也不是很差。

3: Int J Lab Hematol. 2007 Jun;29(3):153-62.
An overview of methods for detection of factor V Leiden and the prothrombin G20210A mutations.
Cooper PC, Rezende SM.
Department of Coagulation, Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, UK.
Venous thromboembolism, represented by deep venous thrombosis and pulmonary embolism, is a common disease with high mortality and morbidity. Within the last 25 years, risk factors for venous thromboembolism have been linked to mutations in the genes of the coagulation/anticoagulation system. Factor V Leiden and the prothrombin G20210A mutations are the most prevalent inherited risk factors predisposing to venous thromboembolism in the Western world. Tests to detect these mutations are carried out when investigating a personal or family history of venous thromboembolism. At the present, there are several different methods available for the detection of these mutations in the laboratory. The choice of the method will depend on many variables. This article is aimed at reviewing the available methods for the detection of factor V Leiden and prothrombin G20210A mutations, their principle, applicability, advantages and disadvantages of use. 本文总结了由Leiden V 和凝血酶原G20210A基因变异导致的易栓症时几种可行的实验室检查方法，应该说关于VTE先天性/遗传性凝血功能障碍的流行病学研究（尤其在欧美）还是很多，但是能顾总结实验室检查方法的文章实在不是很多，本文值得收藏。

4: Arch Mal Coeur Vaiss. 2007 Feb;100(2):133-8.
[Idiopathic venous thromboembolic disease. risk factors for recurrence in 2006]
Christiaens L.
Departement medico-chirurgical de cardiologie, CHU de Poitiers, rue de la Miletrie, 86021 Poitiers Cedex. l.christiaens@chu-poitiers.fr
The duration of anticoagulant therapy after a first attack of venous thromboembolic disease (VTE) is related to the risk of recurrence and the iatrogenic complication of bleeding. Recent prospective trials have provided information concerning the clinical and biological profiles of those at greatest risk of recurrence of deep vein thrombosis. The value of ultrasonic investigations and of D-Dimer measurements have also been assessed. The risk of recurrence is not negligible, about 10% in the first year after stopping treatment and 2/3 of recurrences occurring in the first two years. There are several risk factors for recurrence: male gender, past history of renal transplant, presence of malignant disease, proximal site of the initial thrombosis, initial presentation with pulmonary embolism, previous deep vein thrombosis and the co-existence of two thrombophilic factors. On the other hand, age, single deep vein thrombosis and a family history of deep vein thrombosis are not significantly related to increased risk. The presence of a residual thrombus at the end of treatment remains a subject of controversy. The risk of recurrence when the D-Dimers are normal one month after stopping the anticoagulants seems to be low, especially in cases of an associated thrombophilia. Finally, the risk of haemorrhage is related to the duration of oral anticoagulant therapy and the age of the patient. These trials have provided information for the issue of recommendations by consensus conferences and allow better economic evaluation of the duration of treatment after a first episode of deep vein thrombosis with respect to differing clinical situations.本文是法文，不过流行病学的资料还是比较珍贵，因此推荐一下。

7: Ann Intern Med. 2007 Apr 30; [Epub ahead of print]
Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism. A Randomized Trial.
Ray JG, Kearon C, Yi Q, Sheridan P, Lonn E.
St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
BACKGROUND: Elevated total homocysteine levels are associated with a higher risk for venous thromboembolism. Whether decreasing homocysteine levels with vitamin therapy reduces the risk for venous thromboembolism is not known. OBJECTIVE: To determine whether decreasing homocysteine levels alters the risk for symptomatic venous thromboembolism. DESIGN: Secondary analysis of data from the randomized, placebo-controlled Heart Outcomes Prevention Evaluation 2 (HOPE-2). SETTING: 145 clinical centers in 13 countries. PARTICIPANTS: 5522 persons 55 years of age or older with known cardiovascular disease or diabetes mellitus and at least 1 other risk factor for vascular disease. INTERVENTION: A daily supplement of 2.5 mg of folic acid, 50 mg of vitamin B(6), and 1 mg of vitamin B(12) or matching placebo for 5 years. Measurement: Prospectively diagnosed and confirmed symptomatic deep venous thrombosis or pulmonary embolism. RESULTS: The geometric mean homocysteine level decreased by 2.2 micromol/L in the vitamin therapy group and increased by 0.80 micromol/L in the placebo group. Venous thromboembolism occurred in 88 participants during a mean follow-up of 5 years. The incidence rate of venous thromboembolism was the same in the vitamin therapy group and the placebo group (0.35 per 100 person-years; hazard ratio, 1.01 [95% CI, 0.66 to 1.53]). Vitamin therapy did not reduce the risk for deep venous thrombosis (hazard ratio, 1.04 [CI, 0.63 to 1.72]), pulmonary embolism (hazard ratio, 1.14 [CI, 0.57 to 2.28]), or unprovoked venous thromboembolism (hazard ratio, 1.21 [CI, 0.66 to 2.23]). Limitations: The proportion of patients with a previous episode of venous thromboembolism at enrollment was not known, and venous thromboembolism events were not centrally adjudicated. CONCLUSION: Decreasing homocysteine levels with folic acid and vitamins B(6) and B(12) did not reduce the risk for symptomatic venous thromboembolism. *For a list of the HOPE-2 Investigators, see the Appendix. ClinicalTrials.gov registration number: NCT00106886. Current Controlled Trials registration number: ISRCTN14017017. 本文属于提前发表的文章，而且带着clinical trial的标牌，意义巨大。文章证实通过补充叶酸和维生素B族以降低血液中同型半胱氨酸浓度，进而降低VTE发病率的设想并不可行。

8: J Vasc Surg. 2007 May;45(5):998-1003;
Proximate versus nonproximate risk factor associated primary deep venous thrombosis: clinical spectrum and outcomes.
Henke PK, Ferguson E, Varma M, Deatrick KB, Wakefield GT, Woodrum DT.
Section of Vascular Surgery, University of Michigan, School of Medicine, Ann Arbor, MI 48109, USA. henke@umich.edu
OBJECTIVE: Although the treatment for acute deep vein thrombosis (DVT) is uniform, the circumstances under which it develops vary widely and may impact outcomes. This study compared clinical features and outcomes in patients who developed a primary DVT associated with a defined risk to those without any proximate risk factor. METHODS: Consecutive patients with a primary DVT and no past venous thromboembolism history from 2000 to 2002 were abstracted for demographics, risk factors, DVT anatomical characteristics, treatment, and outcomes of death and new pulmonary embolism. Comparison between patients with a proximate risk event within 30 days of DVT (Inpt) and those presenting with DVT with no defined proximate event (Outpt) was done by univariable and multivariable statistics. A validated survey was mailed to all living patients to assess long-term sequela. RESULTS: A total of 293 patients with a mean age of 55 years and 49% men had confirmed DVT by objective means (92% duplex) with a mean follow-up of 25 +/- 21 months. Inpts were more likely to have recent surgery or blunt trauma, bilateral DVT, less use of low molecular weight heparin (LMWH), and new pulmonary emboli (all P <.05). Outpts with DVT were more likely to have a history of malignancy, tibial-popliteal DVT compared with iliofemoral DVT, higher use of LMWH, and coumadin. However, there was no difference in mortality. From the patient survey (21% response), Outpts were more likely than Inpts to develop later varicosities and have daily frustration related to their legs (P < .05), but no difference in edema or ulceration. Considering the entire group, independent factors associated with freedom from PE included ambulation (odds ratio [OR] = 2.3; 95% confidence interval [CI] = 1.1-5.0; P = .04) while bilateral DVT (OR = .26; 95% CI = .09-.76; P = .013) or subcutaneous heparin (OR = 22; 95% CI = .05-.98; P = .047) were associated with greater risk. Independent factors associated with survival included ambulation (OR = 3.0; 95% CI = 1.3-7.2; P = .02), Coumadin use (OR = 2.7; 95% CI = 1.2-6.1; P = .015), and tibiopopliteal DVT (OR = 2.4; 95% = 1.1-5.5; P = .03), while malignancy (OR = 0.1; 95% CI = .05-.24; P < .01) and myocardial infarction (OR = 0.12; 95% CI = .01-.92; P = .04) were associated with lower survival. CONCLUSION: Patients who develop DVT related to a defined proximate risk event (Inpt) generally have more extensive DVT, an increased risk of PE, but less long-term functional morbidity and no difference in long-term mortality compared to those with no proximate risk.

10: Acad Emerg Med. 2007 May;14(5 Suppl 1):S7-8.
Prospective, Multicenter Validation of the Pulmonary Embolism Rule-out Criteria.
Kline J, Courtney D, Moore C, Kabrhel C, Smithline H, McCubbin T, Richman P, Plewa M, O'neil B, Beam D, Nordenholtz K, Camargo C, Johnson C.

11: Acad Emerg Med. 2007 May;14(5 Suppl 1):S193
Evaluation of 50 potential markers of pulmonary embolism for use in the emergency department.
Mitchell A, Nordenholz K, Kline J. 上面两篇大概是该杂志的年会摘要，不过看题目还是比较有意思的，50个临床标志物！

21: Am J orthop. 2007 Mar;36(3):135-40.
Thromboprophylaxis after hip fracture: evaluation of 3 pharmacologic agents.
Jeong GK, Gruson KI, Egol KA, Aharonoff GB, Karp AH, Zuckerman JD, Koval KJ.
New York University Hospital for Joint Diseases, New York, New York 10003, USA.
We compared the clinical efficacy and side-effect profiles of aspirin, dextran 40, and low-molecular-weight heparin (enoxaparin) in preventing thromboembolic phenomena after hip fracture surgery. All patients admitted with a diagnosis of hip fracture to our institution between July 1, 1987, and December 31, 1999, were evaluated. Study inclusion criteria were age 65 years or older, previously ambulatory, cognitively intact, home-dwelling, and having a nonpathologic intertrochanteric or femoral neck fracture. Each patient received mechanical thromboprophylaxis (above-knee elastic stockings) and 1 pharmacologic agent (aspirin, dextran 40, or enoxaparin); patients who received aspirin were also given a calf sequential compression device. Meeting the selection criteria and included in the study were 917 patients. Findings included low incidence of thromboembolic phenomena (deep vein thrombosis, 0.5%-1.7%; pulmonary embolism, 0%-2.0%; fatal pulmonary embolism, 0%-0.5%) and no difference among the 3 pharmacologic agents in thromboembolic prophylaxis efficacy. Use of enoxaparin was associated with a significant increase (3.8%) in wound hematoma compared with dextran 40 (1.6%) and aspirin (2.4%) (P<.01). The 3 agents were found not to differ with respect to mortality, thromboembolic phenomena, hemorrhagic complications, or wound complications. 本文再一次证实所谓低分子肝素LWMH纯粹是药厂挣钱的噱头，我现在对于LWMH简直恨之入骨。上面的研究发现阿司匹林，右旋糖苷和LWMH在预防骨盆骨折术后的血栓性疾病方面的几个主要指标相当，但是LWMH显著增加伤口出血的风险。

24: Circ J. 2007 May;71(5):772-5.
Unusual pulmonary embolism: septic pulmonary embolism and amniotic fluid embolism.
Sakuma M, Sugimura K, Na kamura M, Takahashi T, Kitamukai O, Yazu T, Yamada N, Ota M, Kobayashi T, Nakano T, Shirato K.
Division of Internal Medicine, Onagawa Municipal Hospital, Onagawa, Japan. m-sakuma@atlas.plala.or.jp
BACKGROUND: Septic and amniotic fluid emboli are rare sources of pulmonary embolism (PE), so the present study sought to elucidate the background of these cases. METHODS AND RESULTS: A total of 11,367 PE cases were identified from 396,982 postmortem examinations. The incidence of septic PE was 247 (2.2%) of the total. The origin of infection was found in 85.6% of the cases. Fungal embolus was detected more often than bacterial embolus. The most frequently detected fungus was aspergillus (20.8%). The primary disease associated with fungal embolus was leukemia (43.2%). The incidence of PE cases associated with pregnancy and/or delivery was 89 (0.8%) of the total PE cases. Among them, amniotic fluid embolism was found in 33 (73.3%) of 45 PE cases with vaginal delivery, and in 7 (21.2%) of 33 PE cases with cesarean delivery (p<0.0001). CONCLUSION: Fungal embolus was more frequent than bacterial embolus, and leukemia was most frequent as the primary disease in cases of fungal embolus. The main cause of PE in cesarean section cases was thrombotic embolism, and the main cause in vaginal delivery cases was amniotic fluid embolism. 本文是来自于日本的，对于几种比较罕见肺栓塞，例如菌栓和羊水栓塞，进行的流行病学调查，资料翔实而准确，我们不仅能看到日本的肺栓塞的统计资料，各能了解罕见的栓塞的分布情况，因此非常值得阅读，由此也能看出我们的差距。研究发现通过近40万例的尸检，肺栓塞发病率为2.86%，在全部肺栓塞患者中，菌栓发生率为2.2%，其中真菌性栓子比细菌栓子常见，真菌栓子中曲霉菌最多见（20.8%）。白血病是导致真菌栓子最主要的病因（43.2%）。此外全部病例中，由妊娠导致的肺栓塞的发病率为0.8%（89例）,其中羊水栓塞多见于阴道生产，剖宫产则以血栓栓塞多见。

30: Clin Drug Investig. 2007;27(5):357-66.
Low-Molecular-Weight Heparins: Before or After Surgery? New Concepts and Evidence : Congress Report from the SIGMA TAU/ROVI Satellite Symposium (Rome, Italy, 13 November 2006).
Rocha E, Imberti D, Paschina E.
School of Medicine, Haematology Service, University Clinic of Navarra, University of Navarra, Pamplona, Spain.
Deep venous thrombosis (DVT) and pulmonary embolism (PE) are potentially life-threatening complications associated with orthopaedic surgery. The choice of an optimal thromboprophylaxis regimen requires full understanding of the efficacy and safety profiles associated with distinct treatments. Low-molecular-weight heparins (LMWHs) are the drugs of choice for thromboprophylaxis in orthopaedic surgery. However, there is concern regarding the timing of LMWH prophylaxis initiation. Among the LMWH molecules, bemiparin has interesting pharmacological properties: the lowest molecular weight, the longest half-life and the highest anti-FXa/anti-FIIa activity ratio. The safety and efficacy of bemiparin administered 6 hours after surgery has been demonstrated in several orthopaedic settings (including major orthopaedic surgery, knee arthroscopy, lower limb trauma and spinal surgery) and during prolonged prophylaxis after major orthopaedic surgery. Another factor to consider in relation to thromboprophylaxis during orthopaedic surgery is the cost effectiveness of bemiparin.The 91st meeting of the Italian Society of orthopaedics and Traumatology (SIOT), held in Rome, Italy, on 12-16 November 2006, provided an exciting opportunity to present new and interesting evidence, including the latest advances in thromboprophylaxis in orthopaedic surgery. Of particular interest were the issues debated during the Sigma Tau/ROVI Satellite Symposium, which focused on the optimal timing strategy for initiating thromboprophylaxis in patients undergoing orthopaedic surgery. This article highlights presentations given during that symposium.

34: AJR Am J Roentgenol. 2007 May;188(5):1246-54.
Time-resolved MR angiography: a primary screening examination of patients with suspected pulmonary embolism and contraindications to administration of iodinated contrast material.
Ersoy H, Goldhaber SZ , Cai T, Luu T, Rosebrook J, Mulkern R, Rybicki F.
Cardiovascular Imaging Section, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St., ASB I-L1-004, Boston, MA 02115, USA. hersoy@partners.org
OBJECTIVE: The purpose of this study was to evaluate the efficiency and reproducibility of a single-breath-hold time-resolved 3D MR angiographic technique in the diagnosis of pulmonary embolism. MATERIAL AND METHODS: Twenty-seven consecutively registered patients with clinically suspected pulmonary embolism and contraindication to administration of iodinated contrast agents underwent imaging by time-resolved 3D MR angiography at 1.5 T. Bolus timing was not required. Two reviewers independently analyzed MR angiograms for overall image quality and evidence of pulmonary embolism. Additional imaging techniques, including pulmonary embolism CT angiography, ventilation-perfusion (V/Q) lung scanning, venous duplex sonography for deep venous thrombosis, and echocardiography for right ventricular strain, and 30-day and 3-month clinical follow-up were used to confirm the MR angiographic findings. RESULTS: Image quality was sufficient for diagnosis in the cases of 98% of lobar, 92-93% of segmental, and 94-95% of all vessel parts from the main pulmonary artery though the segmental branches with excellent interobserver agreement. Findings on MR angiography were concordant with the anatomic distribution of abnormalities for all pulmonary embolism CT angiographic examinations (n = 2) and four of seven V/Q lung scans. Screening with time-resolved 3D MR angiography allowed confident exclusion or inclusion of pulmonary embolism in 96% of patients. CONCLUSION: Time-resolved 3D MR angiography provides high temporal resolution (nine phases, one phase per 3.3 seconds) and consistently yields arterial phase only images. As found with clinical follow-up, confident diagnosis of pulmonary embolism from the main pulmonary artery through the segmental branches can be incorporated into a clinical service as a screening examination of patients with contraindications to the use of iodinated contrast material. MRI进入肺栓塞一线检查方案从目前的趋势看是迟早的事情，尽管目前其应用尚集中于某些造影剂过敏的疑诊患者，但其实际的应用价值、影像质量和速度绝对不会低于多层螺旋CT的，目前正在进行的PIOPED 3期研究将在未来1-3年内完成，可以说PIOPED首期研究讨论的是通气灌注扫描，2期研究是去年发表在NEJM的多层螺旋CT，3期研究目前正在进行，我们拭目以待。

36: Ann Emerg Med. 2007 Apr 19; [Epub ahead of print]
Thrombolytic Therapy for Submassive Pulmonary Embolism?
Worster A, Smith C, Silver S< /a>, Brown MD.
Division of Emergency Medicine, McMaster University, Hamilton, Ontario, Canada.
STUDY OBJECTIVE: The purpose of this review was to determine the effectiveness of adding thrombolytics to standard heparin therapy for treatment of submassive pulmonary embolism. Patients with submassive pulmonary embolism were considered to be those with evidence of right ventricular dysfunction but without hemodynamic instability. METHODS: We searched for trials comparing thrombolytics to heparin in the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. We included only studies assessing the effectiveness of thrombolytic therapy for submassive pulmonary embolism and reported the patient-important outcomes of mortality, recurrent pulmonary embolism, and major hemorrhage. RESULTS: Two randomized trials met the inclusion criteria; one with a total of 256 patients presenting with submassive pulmonary embolism and the other trial including a subgroup of 46 patients with submassive pulmonary embolism. In the larger study, the relative risk (RR) for mortality, recurrent pulmonary embolism, and major hemorrhage was 1.56 (95% confidence interval [CI] 0.36 to 6.83), 1.17 (95% CI 0.30 to 4.57), and 0.23 (95% CI 0.03 to 1.97), respectively. Our post hoc subgroup analysis of the smaller trial identified 2 deaths and 5 patients with recurrent pulmonary embolism among 23 controls, whereas none of the 23 patients randomized to thrombolytics died or had recurrent pulmonary embolism. None of these findings were statistically significant. CONCLUSION: Results of randomized trials comparing the addition of thrombolytic therapy to standard heparin therapy for treatment of submassive pulmonary embolism fail to show any significant differences in clinically important outcomes. 关于肺栓塞的亚大块血栓的溶栓问题一直是目前的热点，这是一篇荟萃分析，本次的结论还是不建议溶栓。不过我现在越来越觉得荟萃分析的机械性，每一个病人的病情都是个体化的，而每一个个体化的特征都和治疗以及预后有着密切的关系，荟萃分析不可能所有的重要的特征都能顾及到，即使顾及到，也不可能每个特征都进行亚组的分析，因此由荟萃分析得到的结论也绝对不是所谓的最科学理性的，同样的道理，对那些大样本，多中心的研究也要慎重对待。不过这里我并不是说我支持亚大块肺栓塞溶栓。我只是觉得现在言必称荟萃，系统综述有点太小儿科了。越来越多的例子已经证实荟萃分析有的时候也是胡说八道。眼前的例子就是关于白蛋白的系统综述的，两组人马先后进行的荟萃分析得到了几乎相反的结论，到后来两组人马互相嘶咬起来（我以前的危重病医学导读已经谈过）。另一个例子就是多层螺旋CT诊断肺栓塞，我记得到目前为止也没有哪篇荟萃能够完全证实多层螺旋CT可以用于疑诊肺栓塞的首诊（问题出在亚段血栓的诊断精确度上），不过环顾国内外，好像临床上也没有谁敢在疑诊肺栓塞时不做多层螺旋CT的，即使理论上床边彩超也是可行的，无论我在德国还是在国内，主治医生最先想到的还是大队人马杀奔CT造影，即使患者已经开始人工辅助通气也在所不惜（在德国尤其如此）。这就是现实，因此让那些荟萃分析见鬼去吧。

无反应肺炎（Noresponding pneumonia）

amicacin@gmail.com(Amic) — Fri,27 Apr 2007 12:50:50 +0800

2007年美国胸科协会（ASA）和感染协会（IDSA）的CAP指南中正式提出无反应肺炎（Noresponding pneumonia）的概念。这在ICU应该不少见，所以具有重要参考意义。这里是协和医院呼吸内科蔡柏蔷教授的导引。

无反应肺炎定义
    目前，无反应肺炎定义为在接受抗感染治疗的情况下，CAP患者没有获得显著改善的一种临床情况。既往曾经将无反应肺炎定义为抗生素治疗至少10日后，仍有肺部浸润阴影以及肺部急性感染的临床表现(例如：持续发热 >38度，伴有不适、咳嗽和／或呼吸困难)，临床状况无改善或恶化；或者肺炎发病12周后影像学表现为肺部阴影无吸收。进展型肺炎定义为抗感染治疗24小时后临床表现恶化、且影像学上表现为肺部阴影增加50％以上，或者治疗 72小时后临床上出现需要通气辅助治疗的急性呼吸功能不全和／或感染性休克的状态。
    临床上无反应肺炎病例并不少见。总的来看，6％—15％的CAP患者对于最初的经验性抗感染治疗无效。在一组 444例的CAP病例的临床研究中，49例(11％)CAP病例经验性抗感染治疗无效。其中30例(61％)为无反应肺炎， 19例为进展型无反应肺炎(39％)。49例患者中发病初即为重症CAP，共16例 (33％)，急性呼吸衰竭需要呼吸机辅助通气治疗9例(56％)，感染性休克2例 (13％)。
    分类 2007年IDSA和ATS对无反应肺炎的分类如下(表1)。这是—种根据距离起病的时间和肺炎无反应性的类型，对可能病因进行系统性分类的方法。

    根据定义，所有CAP患者中，无反应肺炎主要行两种类型。第—种是进展型无反应肺炎，即临床表现为进行性恶化的肺炎。其中—部分是初治重症CAP患者，患者通常在发病72小时之内出现急性呼吸衰竭需要机械通气和／或存在感染性休克，因此具备进入ICU的指征。另一部分进展型患者则足在其他科室治疗过程中由J：病情恶化而具备进入1CU指征的，这部分患者—般发病超过72小时，呼吸衰竭和低血压的情况多数是由于治疗过程中出现的并发症导致的，据统计，在最终有进入 ICU指征的所有CAP患者中，约45％的病例都属于此类。
    第二种类型的特点是病情呈持续性或无反应。另外，既往曾经把出现 CAP症状后肺内浸润阴影持续大于30天的肺炎称为无反应或慢反应性肺炎，这类患者中，20％患者在重新评估后能发现CAP以外的疾病。
    原因表1有助于逐步推断导致无反应肺炎的潜在原因。无反应肺炎病因中感染性因素占到约40％，致病病原体包括耐药菌(如肺炎链球菌、金黄色葡萄球菌、铜绿假单孢菌)，军团菌，少见病原体(如结核分枝杆菌、曲菌／真菌、奴卡氏菌、肺孢子菌)；非感染性因素占约15％，主要原因有新生物、肺出血、肺水肿、闭塞性支气管炎伴机化性肺炎(BOOP)、嗜酸性肺炎、药物诱发浸润和肺血管炎；此外，其中病因不明者占45％。
CAP病例研究中，无反应肺炎的发生率为15.1％，造成肺炎无反应性的原因为感染性因素的占40％，非感染性的为 15.8％，其他为原因不明确。经过逻辑回归分析，成为独立相关危险因素的因子有肝病、肺炎高危群体、粒细胞减少、多叶渗出、胸腔积液、影像学空洞和 COPD等。

对治疗无反应肺炎的判断
无反应肺炎的临床特点表现为，没有或延迟达到临床稳定状态(即：体温37.8度；心率≤100次／分；呼吸频率≤24次／分；收缩压 90mmHg；在呼吸室内空气时血氧饱和度 90％或血氧分压 60mmHg；正常经口进食；意识状态正常)。因此在治疗的前72小时一般不作出无反应肺炎的诊断，只有在病情恶化或有新的病原体培养资料或流行病学调查提示其它病因时才考虑在这一阶段更改抗生素治疗。

无反应肺炎的处理
CAP仍沿用经验性治疗。如何处理这些对常规治疗无反应的患者是经验性治疗面临的难点。经验性抗感染治疗失败时，应重新对患者进行全面的临床评估，深入病原学及影像学检查。抗菌治疗应覆盖更为广泛的病原菌，力求达到对不典型病原体及耐药病原体感染的控制。
    临床评估对于临床无反应肺炎的病例应按照以下临床途径进行评估。 (1)重新考虑CAP的诊断是否正确，是否存在以肺炎为表现的其他疾病，如肺血管炎等。(2)目前治疗针对的病原是否为致病病原，是否有少见病原体如分支杆菌、真菌／曲菌等感染的可能性。 (3)目前针对的病原体是否可能耐药，判断用药是否有必要针对耐药菌进行升级。(4)是否有机械性因素如气道阻塞造成的抗感染不利情况。(5)是否忽视了因该引流的播散感染灶，如脑脓肿、脾脓肿、心内膜炎等。(6)是否存在药物热可能性。
    实验室检查 (1)病原学检查：根据临床评估的步骤，重新评价病原学证据是明确诊断的重要措施。CAP最常见的病原和病因依次为肺炎链球菌(22％)，军团菌(21％)，流感嗜血杆菌(5％)，吸人性肺炎(6％)。无反应肺炎中军团菌及革兰氏阴性菌为常见病原体。另外应重视有关非典型病原体感染可能性方面的病史。病毒性肺炎在成年人诊断中常被忽略，但其比例可达10％—20％。病原学的检查手段分为有创检查(支气管镜下保护性肺毛刷、肺泡灌洗液、活检等)和无创检查(痰培养、血培养、血清抗原、尿抗原、其他培养等)。这些检查可使 73％的无反应性CAP患者获得特异性的诊断。临床上应该重视无反应肺炎的危险因素，对于发病之初就具有显著性危险因素的患者，应该在尽早开始进行更加积极的诊断性病原学检查。(2)胸部CT：除了可提示肺栓塞外，还可以揭示其他抗感染失败的原因，包括胸腔积液，肺脓肿或者中心气道阻塞。阴影的形态也可以提示非感染性疾病，如闭塞性细支气管炎伴机化性肺炎等。(3)胸腔引流：气胸及肺炎旁胸腔积液也是较常见的造成无反应肺炎的原因，无论有无明显的胸腔积液都应该进行胸腔引流，并进行病原学检查。(4)支气管镜检查，经支气管镜肺泡灌洗和经支气管镜肺活检：如果无反应肺炎的鉴别诊断中包括某些类似肺炎的非感染疾病，应该进行支气管镜检查以提供更多的诊断资料，并且可进行常规微生物学培养。经支气管镜肺泡灌洗能够发现非感染性疾病，例如：肺泡出血或嗜酸性肺炎。
    抗生素的应用无反应肺炎抗生素的应用尚无研究的报道。因为未覆盖感染病原体的经验性治疗是预后不良的影响因素，所以在获得有诊断意义的病原学检查结果前，经验性治疗的抗生素方案应该相应充分。不充足的经验性治疗对患者预后可造成不良影响，故抗菌治疗应尽可能的增加对病原体覆盖，尤其是重症CAP病例。对于无反应肺炎抗生素的治疗，应根据不同地区的抗生素耐药情况及患者病史进行综合考虑：(1)是否有必要应用抗铜绿假单孢菌的p—内酰胺类药物；(2)优先选择氟喹诺酮类药物；(3)如果患者存在重症CAP或长期免疫抑制情况(如临床应用糖皮质激素)应考虑是否开始抗真菌治疗；(4)根据病史提示、临床表现分析是否开始针对少见病原体(如肺孢子菌、奴卡氏菌等)的治疗。
    总之，无反应肺炎是由于特殊的病原体和宿主异常的免疫状态相互作用造成的。对于无反应肺炎的诊断治疗，首先应确定诊断无反应肺炎的时机，只有及时的正确诊断，才能开始及时的治疗。其次应明确无反应肺炎的分类，目前根据时间及病因分类的方法可以提供病因诊断的线索。再次，每个CAP患者都需要进行规律的病原学检测，尤其要重视具有无反应肺炎危险因素及重症CAP的病例。最后无反应肺炎的抗菌治疗时应在综合临床和病原学证据的基础上，尽可能地覆盖病原体。

黄教授专栏：《德国医学教育的POL模式》

amicacin@gmail.com(Amic) — Sun,01 Apr 2007 19:52:36 +0800

在德国做临床培训，自然就接触到德国的医学生和医学教育。最近我的老师每周都要去带“POL”，我也就跟着旁听，觉得这种医学教育模式非常好，介绍出来给大家了解。也许国内已经有开展了。

POL就是“Problem orientiertes Leren”翻译过来就是“以问题为主导的学习”，这和美国/加拿大的PEL/CBL非常紧似，后者是Problem-Based Learning/Case Based Learning ，即根据问题/病例学习，PBL是1960年在加拿大发展起来的医学教育模式。

其过程简单的说，就是以6-8人为一组，每周一般两次课，每次2个小时，课程安排在专门的POL教室。第一节课开始每个学生会得到只有数行字的“病情介绍”。其内容和格式非常随意，比如以医生的口吻回忆某天在门诊看到一个什么样的病人，病人说了什么（往往是日常用语，而不是医学主诉形式）；或者就像小说的开场白一样，描述了两个邻居之间的一段有关自己病情的对话。就这么简单的几句话！

之后学生会自觉从专门的POL学习箱中取出纸片和水彩笔，各自写下自己的印象诊断和下一步需要的检查，一般都尽可能考虑得多一些。之后大家依次讲解自己的诊断，并把自己的纸片用图钉钉在专用的演示板上。有的时候是只用一张大纸大家依次边说边写，然后钉在演示板上。

上一步完成后，老师就扮演病人，一个同学会主导开始问诊，（老师手上会有该病人详细的病例和几乎所有需要的的辅助检查结果，以及彩色病理照片或影像结果），老师会全真模拟病人的情况，只回答问过的问题，绝不会引导学生下面还要问什么或继续做什么，对于老师无法提供答案的问题，比如问到病人的亲戚患病或迁移情况，老师会说不知道的或者“没提”。其他的学生在之后会补充问一些问题，临床的全部问题基本结束之后，才会问到检查结果，老师还是问到什么告诉什么，不会把所有的结果依次宣读的，随后大家会再考虑诊断和检查的问题。

最后学生们会看病理照片或影像结果，但上面不会注明诊断（老师经常会把病理描述念给大家，但不会说诊断，下图就是学生们看病理图片）。

最后学生们讨论诊断，分析病因和讨论下一步的诊治计划。这个时候一般能得出准确的诊断。不过有的时候病例很罕见，到最后学生们还各执己见或者茫茫然。这时老师会问学生要不要知道答案，如果学生说要，老师才会告知答案。

这个时候，可并没有结束。马上会有学生在另一个演示板上写出与病机、诊断、治疗等方面的需要进一步讨论和学习的问题，大约7-8个主题，其他学生补充。然后每人3票，分别选3个主题，如果某人觉得某个主题特别重要，可以用两票投一个主题，最后计算每个主题的得票数，得票最多的前3个问题最为第二节课的讨论的内容。第二次课和首次课之间一般会有4-5天的间隔，以便于学生充分自学，掌握相关材料。

其他的细节还包括：

老师不是课程的主角，每次课很少会主动讲话，基本是组织协调，不参与讨论。

病例是由各科提供，所有的材料集中在一个档案袋中，学生只有“病情介绍”，其他的临床资料只有一份，掌握在老师那里，课后上交到POL办公室，学生们到最后也看不到全部的材料，好像也没有人主动要求看这份材料的。而且上课的病例和老师的专业并不相关。比如我们连续讨论了3周皮肤科的疾病，而我的老师是麻醉与监护科。

实际上POL是一个很深奥的教育学范畴，比如下图就能说明PBL是一个不断循环的过程，而主题式学习只是单向的。我上面讲的只是表面文章，如果有兴趣可看：

http://images.google.com.sg/images?num=100&hl=zh-CN&newwindow=1&rls=GGLJ,GGLJ:2006-38,GGLJ:zh-CN&q=Problem-Based%20Learning&btnG=%E6%90%9C%E7%B4%A2&ie=UTF-8&oe=UTF-8&sa=N&tab=wi

http://www.uni-koeln.de/ew-fak/konstrukt/didaktik/problembased/begruendung.html

和http://www.cimwareukandusa.com/All_Cases/CaseBasedLearningWeb.html，或者在GOOGLE上搜索一下，很多的。

NEJM:衰竭的心脏是一台缺乏燃料的发动机

amicacin@gmail.com(Amic) — Thu,22 Mar 2007 12:13:45 +0800

    心力衰竭是一个巨大的医学和社会负担。它是——种常见病：2％的美国人群或近500万人受累，30％—40％的患者在诊断后的1年内死于心力衰竭。心力衰竭可使患者失能，严重降低患者的生活质量。心力衰竭在英国约消耗国家卫生服务局预算的2％，在美国，每年用于治疗心力衰竭的总费用接近28.0亿美元。另外，随着社会的老龄化以及对心力衰竭病因治疗的进步，预计心力衰竭(造成)的财政负担在今后的数十年将会增加。
    在过去的20年里，使用血管紧张素转换酶(ACE)抑制剂、醛固酮拮抗剂、B受体阻滞剂和心脏再同步化治疗，使慢性心力衰竭的治疗取得了很大进步。然而，即使采用了最先进的治疗措施，心力衰竭的年死亡率仍然为10％。寻找更好的治疗措施是心脏病学领域的主要挑战之一。
    慢性心力衰竭是一种多病因疾病。很多原因可以导致人类的心脏衰竭，但是现有证据提示，衰竭的心脏是一台缺乏燃料的发动机——即能量代谢的改变在心力衰竭的发病机制中起重要作用。因此，调节心脏的代谢有可能成为心力衰竭治疗中的一种新方法。
    本综述描述心脏的能量代谢，评价其评估方法，评估能量代谢受损在心力衰竭中的作用，并提供有关代谢疗法的一些选择方案。
    能量饥饿假说
    数十年前就有人提出了衰竭的心脏是一台缺乏能量的发动机的概念。
    这一概念是 lIerrmann和Decherd在1939提出的，他们在题为《心力衰竭的化学本质》一文中指出，衰竭的心肌中肌酸含量显著减少。在随后的20年里，很多学术团体在此基础上提出了能量耗竭假说。今天，心脏的能量代谢——心肌能量学——成为引起人们极大关注的热点之一。心肌能量学受到关注的主要原因是，任何减少能量消耗的心力衰竭疗法，如B受体阻滞剂、ACE抑制剂或血管紧张素Ⅱ受体阻滞剂。均可改善患者的预后。衰竭的心脏被比作一匹衰弱和疲惫的马，如果给马提供适当的营养，它就可以恢复并工作很长时间，尽管工作效率减低。

心脏的能量代谢
    心脏能量剥夺在心力衰竭中起主要作用。心脏耗能比其他任何器官都大。它周而复始地工作，每天约消耗6kg ATP——是其自身重量的20-30倍。心脏每天约跳动10万次，约向全身泵出10吨血液。为获取必需的能量来执行其功能，心脏将储存在脂肪酸和葡萄糖中的化学能，转化为肌原纤维中肌动蛋白—肌球蛋白相互作用的机械能。不能产生足够的能量就会导致心脏发生机械故障。
    心脏能量代谢的组成部分
    心脏的能量代谢是复杂的(图1)。代谢装置有3个主要组成部分。第1部分是底物利用——使用来自食物的燃料。这一过程主要包括细胞摄取游离脂肪酸和葡萄糖，通过B氧化和糖酵解将其分解，随后中间代谢产物进入三羧酸循环。第2部分是氧化磷酸化——线粒体的呼吸链产生能量。ADP通过此机制磷酸化，产生高能磷酸化合物ATP，ATP是心脏所有耗能反应中使用的直接能量。第3部分是ATP的转运和利用——将能量转运至肌原纤维和能量被心脏的发动机肌原纤维消耗。这一过程所必需的能量转运机制被称为肌酸激酶能量穿梭。
肌酸激酶系统
在心脏能量代谢的第3部分中， ATP转运和利用，线粒体肌酸激酶催化将ATP中的高能磷酸键转运至肌酸中，形成磷酸肌酸和ADP。磷酸肌酸是比ATP小的分子，很快由线粒体弥散入肌原纤维，肌原纤维肌酸激酶催化磷酸肌酸重新形成ATP。从磷酸肌酸中去除磷酸后形成的游离肌酸，通过弥散方式回到线粒体。
    肌酸由肝脏和肾脏产生，被转运至心脏，在心脏中被特殊的浆膜肌酸转运体摄取，这一过程需要逆50倍的浓度梯度。肌酸激酶催化心脏总肌酸池中约 2／3的肌酸磷酸化，产生肌酸磷酸，其余 1／3仍为游离肌酸。少量肌酸通过肌膜被动弥散，不断地从心脏中移出。肌酸激酶系统的一个重要功能是作为能量缓冲物。当能量需求超过能量供应时，磷酸肌酸水平下降，使ATP保持在正常水平，但游离ADP水平升高。游离 ADP水平升高可抑制很多细胞内酶的功能，引起心脏收缩机制的功能衰竭。因此，当磷酸肌酸水平下降，ADP水平升高时，即使ATP水平保持不变，心肌细胞仍可发生能量代谢紊乱。

心脏能量代谢的评估
可通过采用标准的方法来测定心脏能量代谢的各种成分，用于测定能量代谢的心肌标本可来自活检，或在心脏移植中获取，或来自动物的心脏组织。然而，分析组织标本中的ATP和磷酸肌酸是一个难以解决的问题，因为这些分子是不稳定的。基于此原因，检测 ATP和磷酸肌酸的主要方法是P磁共振(31p_MR)光谱分析。此方法在啮齿类动物中可使用到12．0特斯拉(Tes 1a，磁场强度的指标)的高磁场，在人类可用标准的临床磁共振成像(MRl)系统 (通常为1．5特斯拉)。如图2A所示，P— MR光谱产生磷酸肌酸和ATP 3个磷原子(叩-ATP、ct-ATP和p-ATP)的峰，这些峰与这些代谢产物的浓度成比例。MRI系统可获得心脏的电影图像，并同时对心功能进行定量。心力衰竭时评估能量代谢最有效的方法，是在体内评估葡萄糖和脂肪酸的转换率以及氧化磷酸化率和ATP的转运率。方法学中的一个重要问题是细胞区隔化。一个心肌细胞的功能是否正常，不能通过测量ATP、磷酸肌酸或ADP的平均细胞水平来确定，但可通过测定它们在肌原纤维周围间隙中的浓度和肌质阿附近以及肌原纤维膜离子泵附近的浓度来确定。目前还没有测定这类指标的方法，因而只能从总测量值中推断。

    心力衰竭时的能量代谢紊乱
    心力衰竭时的心脏能量代谢改变见图3，图中总结了在动物模型中和在心力衰竭临床研究中的所见。这些变化发生在心脏能量代谢的3个部分：底物利用、氧化磷酸化和高能磷酸化合物代谢。
    底物利用
    心力衰竭时，由于底物摄取和(或)氧化减少，底物的利用可能对心功能造成限制。这也可能是脂肪酸(60％- 90％)和葡萄糖(10％-40％)对ATP合成的贡献发生了改变的结果。人们在心力衰竭时底物利用的研究中得出的结果相互矛盾，但是多数研究提示，脂肪酸利用在早期心力衰竭时没有改变或轻度增加，但在严重心力衰竭时显著减少。有关葡萄糖利用的改变的研究结果也不一致，但是很多研究显示，葡萄糖利用在早期心力衰竭时是增加的。严重心力衰竭时，心肌产生胰岛素抵抗，多数研究显示葡萄糖利用减少。然而，心力衰竭时常见血浆游离脂肪酸、葡萄糖和胰岛素浓度明显升高，这使得对上述研究结果的判读变得复杂。这些物质水平的升高，使得人们很难区分心肌本身代谢通路容量的改变与代谢环境改变引起的心肌的间接变化。
氧化磷酸化
氧化磷酸化受损时，由于不能给心肌细胞提供充足的ATP而使心脏功能降低。心力衰竭时，心肌细胞线粒体存在结构异常，数量很可能增加。电子转运链复合物的活性和ATP合成量均下降，受磷酸基团接受体ADP、 AMP和肌酸调节的氧化磷酸化受损，解耦联蛋白(使线粒体产生热，而不是 ATP)的水平有可能升高。这些改变在衰竭心肌中导致氧耗量和能量的产生明显减少。
    高能磷酸盐代谢
    ATP转运和利用受损有可能通过下列途径来限制心肌收缩功能：降低平均ATP浓度，减少肌酸激酶作用下的 ATP转运量，从而导致从线粒体转运到肌原纤维的高能磷酸键不足，或增加游离ADP浓度。
    在发生严重心力衰竭前，心肌ATP水平保持正常(约10mmol／L)，严重心力衰竭时其水平下降不超过30％~40％。心力衰竭时的平均ATP水平，远高于消耗ATP的反应如肌球蛋白-ATP酶所需要的ATP水平，而且不会限制收缩功能。然而，磷酸肌酸和总肌酸水平在较早期阶段就下降，而且幅度较大(30％～70％)。心力衰竭时肌酸转运体功能下调，导致总肌酸和磷酸肌酸水平下降。
    心力衰竭时肌酸激酶系统有明显改变。线粒体肌酸激酶的活性可降至正常活性的20％，肌原纤维肌酸激酶的活性可下降到正常值的50％。高能磷酸化合物减少和肌酸激酶活性下降导致ATP转运严重下降－－即细胞内能量流减少——于是，转运至肌原纤维的能量最多可减少71％。这种代谢异常有可能引起收缩功能障碍，尤其是导致收缩功能储备减少，后者是心力衰竭时心肌的特征。
    当衰竭的心脏受到儿茶酚胺刺激时，心脏工作负荷增加，游离ADP浓度增加至接近正常心肌的两倍。高工作负荷情况下，相关微小分隔区内(肌原纤维周围，肌质网附近和肌原纤维膜离子泵附近)游离ADP的增加，减少了衰竭心脏的收缩功能储备，这种收缩功能储备减少在临床上表现为劳力性呼吸困难。
    有关人类心力衰竭时心肌能最代谢紊乱的多数证据，来自P-MR)光谱学研究。这种方法可用于确定磷酸肌酸：ATP比值，这是心脏能量状态的—个强效指标。肌酸激酶反应平衡对 ATP合成比对磷酸激酸合成更有利，前者比后者高约100倍，因此，当对 ATP的需求大于ATP合成时，磷酸激酶水平首先下降，只有在磷酸激酶明显耗竭时，ATP才下降。然而，在慢性心力衰竭时，第2种机制起作用：总肌酸水平下降，这进一步降低了磷酸肌酸：ATP比值(图2)。心肌磷酸激酶： ATP比值在心力衰竭时下降，它们与纽约心脏学会的(心功能)分级以及收缩功能和舒张功能指数相对应。一项研究纳入了39例扩张型心肌病患者，结果提示，与功能性或临床参数相比，磷酸肌酸：ATP比值可能是总死亡率和心血管病死亡率的更强预测因子(图2B)，但是此发现需要得到更大规模临床试验的证实。
    肥厚型心肌病是心肌能量耗竭的一个典型例子。在肥厚型心肌病患者中，由于发生一系列累及肌节的特殊突变，导致心脏磷酸激酶：ATP比值降低，不论患者是否存在左心室肥厚。因为能量代谢异常是原发性心肌疾病的早期和不可缺少的改变，所以，我们可以推断心肌能量代谢受损在肥厚型心肌病中具有病因的作用。能量代谢的分子调节物
    在心脏发育过程中和住生理性或异常应激的情况下，心脏的能量需求有很大变化。能量产生必须与能量需求紧密适配，但心脏的底物储备量很少。然而，机体有诱导编码能量代谢的分—广调节物基因表达的机制。
    核受体转录因子
    脂质代谢产物激活几种核受体转录因子的方式，类似于类固醇激素对核受休的激活。在不断变化的底物环境中，这些转录因子迅速与基因表达耦联，其作用通常需要辅助激活因子蛋白的参与。这些转录因子中，研究最广泛的是过氧化物酶体增殖物激活受体 (PPAR)家族的核受体，由3种业型组成：PPARa、PPARB和PPARr。3种亚型都影响心脏脂质代谢，但是主要的调节物是PPARa，它控制直接参与脂肪酸氧化的酶的表达。在动物模型“和人类心脏肥厚时，PPARa的表达减少与脂肪利用下降成比例。因此，PPARa下调被认为是导致底物利用由脂肪酸转为葡萄糖的主要机制。这种转换是肥厚的心脏的特征。
    核受体辅激活因子，PPARr辅激活因子—1(也称为PCG-1a)，是线粒体代谢功能的一个主要调节物。它激活负责脂肪摄取和氧化以及负责氧化磷酸化的多种基因。这些基因包括 PPARa和PPARB以及核呼吸因子1和2。实验研究提示，PCG—1a受抑制，很可能是高血浆儿茶酚胺水平的直接后果，可引起线粒体基因表达的下调。它在衰竭的心脏中以此种方式导致氧化磷酸化受损。PCG- 1a缺乏加速了心力衰竭的进展，提示这种辅助调节物可能有心脏保护作用。
    尽管取得了上述进展，仍然需要开展更多工作才能完全了解代谢性信号传导中的哪些变化是适应性的，哪些是适应不良性的，或哪些兼有上述两种特性(取决于心力衰竭的分期)。另外，心力衰竭时肌酸转运和肌酸激酶表达的分子调节物的变化还不清楚。

基因敲除模型和功能丧失性突变
人们对能量代谢改变在心力衰竭中的病因性作用已经争论了数十年，目前仍未解决。一种有希望得到肯定答案的方法是研究选择性敲除某种基因成分的基因调控小鼠，选择性地敲除(功能丧失)代谢过程中的基因成分，或导致人类单基因先天性代谢缺陷的基因成分。表1列出了人们在小鼠模型和人类中研究过的基因异常，同时列出了相应的心脏代谢和功能性表型。编码参与底物利用、氧化磷酸化和高能磷酸化合物代谢的特殊代谢成分的多种基因的缺失，可引起收缩功能储备减少，明显的心力衰竭，心脏肥厚，快速性心律失常或缓慢性心律失常。这些基因研究显示，代谢机制完整对维持正常心脏功能非常重要，选择性消除能量代谢中的某些成分可引起早期或严重心力衰竭然而，这些基因研究的长处也是其弱点，因为慢性心力衰竭是多因素造成的，包含很多机制，并非只受所研究的单基因控制。另外，我们还不了解一个编码在心脏能量代谢中起核心作用的高度保守蛋白的基因，是如何缺失的，而且(其缺失)并未引起明显的心力衰竭(表1)。一种关键代谢成分的缺失是否会引起适应性变化以及适应性变化的程度还不清楚。

对心力衰竭治疗的意义
ACE抑制剂、利尿剂和B阻滞剂可能对心脏代谢有间接影响，但它们不会直接影响能量代谢。能量代谢能够成为心力衰竭患者治疗的特殊靶点吗?
调节底物利用对心力衰竭患者进行代谢干预的一个有前景的策略是调节底物利用，一项研究纳入了8例心力衰竭患者，向冠状动脉内输入丙酮酸盐可在短期内改善心脏功能：在一个狗的心力衰竭模型中，通过使用胰升血糖素样肽1增加葡萄糖的利用，可改善左心室的功能。另外，在小鼠的心力衰竭模型中，转基因过表达葡萄糖转运体1，可预防左心室功能不全的发生。
使用脂肪酸氧化的部分抑制剂或肉毒碱棕榈酰转移酶1抑制剂，直接操控底物的利用是可行的。这些化合物有多种作用，但是它们都可部分抑制脂肪酸的利用和促进葡萄糖的利用。人们对心力衰竭时抑制脂肪酸氧化是有利还是有害这一问题有很大争议，心力衰竭的病因或分期有可能决定这种治疗的结局。无论理论上的争论如何，近期许多概念验证性临床研究提示，部分抑制脂肪酸的氧化是有希望的。例如，使用脂肪酸氧化抑制剂曲美他嗪 (trimetazidine)治疗，可使老年患者的左心室功能改善6个月。一项历时18个月的研究在心肌梗死后心力衰竭患者中证实了上述研究所见。小规模单中心研究和迄今未获证实的研究显示，缺血性或非缺血性心力衰竭的患者使用脂肪酸氧化抑制剂哌克昔林(perhex iline)治疗2个月或用肉毒碱棕榈酰转移酶1抑制剂etoxomirn6治疗3个月，可改善左心室射血分数。对这些小规模研究的结果应当慎重判读。一些研究并没有在随机、盲法或有安慰剂对照的条件下实旌，另外一些研究纳入了心绞痛患者，这可部分解释抑制脂肪酸氧化的有益效应。但是，它们为这类抑制剂在动物心力衰竭模型中效应研究的结果提供了支持

PPAR 活化剂对心肌底物利用的影响是复杂的。其效应包括直接上调脂肪酸氧化，以及通过降低血脂水平间接下调脂肪酸氧化。有人发现，发生PPARct过表达的小鼠可发生心衰，PPAR活化剂在动物心衰模型中有可能产生有益作用、有害作用或没有任何作用，这些结果提示，需要在更深入地了解这些化合物在衰竭心脏中的作用后，才能考虑进行较大规模的临床研究。
调节氧化磷酸化 心力衰竭代谢治疗的第二种策略是直接刺激氧化磷酸化。然而，目前还没有氧化磷酸化的有效调节剂。即便如此，以增加PCG-la的活性作为上调氧化磷酸化酶的方式，可能是一种有前景的方法。另一种备选方法是降低游离脂肪酸的水平，抑制线粒体解耦联蛋白，从而增加ATP的合成。
操控高能磷酸盐代谢物
代谢干预的第三种策略是直接操控高能磷酸盐的储存、利用度或利用的效率。可通过提高肌酸转运体的功能来提高肌酸和磷酸肌酸水平。虽然大幅度提高肌酸转运体的功能是有害的(因为明显高于正常的肌酸水平可增加游离 ADP水平)，但未来的研究将使人们明确，通过中度刺激肌酸转运体的活性来逆转肌酸和磷酸肌酸水平的降低，是否对心力衰竭(患者)有益。最后，使用新型钙增敏剂lN或肌球蛋白激活剂复合物，提高肌原纤维对ATP的利用效率可能是可行的。

结论
代谢疗法是治疗心力衰竭的一种有前景的新途径，合适的治疗靶点是底物利用、氧化磷酸化和提供高能磷酸化合物。对此概念的充分研究还需进行多方面的努力。例如，实验性研究将进一步澄清导致能量代谢紊乱的机制，并提示治疗性干预的新分子靶点。新的代谢调节化合物需要由学术界和企业来研发。概念验证性临床研究有可能使用心肌磷酸肌酸：ATP比值来监测心脏对代谢治疗的早期能量代谢反应，这种方法有可能提供预测远期预后效果的替代指标。最后，大规模临床研究将证实或推翻代谢调节剂的临床疗效。这种综合性的努力很有希望导致靶向心脏能量代谢的新疗法的出现。这些治疗方法有可能改善慢性心力衰竭患者的症状和预后。

(原文：http://content.nejm.org/cgi/content/full/356/11/1140)