huangwei98，想不想家？

本周文献概述

首先说一下最近老黄身体的事情——经过柏林wedding区唯一一个肺科医生Dr.Mahlo D-H的漫长诊断（所以他的门诊人满为患，我还以为到第三世界缺医少药的地界去了，不过还是要赞一下人家的门诊，血气，血常规，胸片，肺功能+最后的过敏原皮试都是一气呵成的），本人铁打的标准亚洲体块竟然对全球性生长分布的桦树以及桤木呈强阳性（++++）皮试反应！而这两个宝贝树种的“高峰喷发期”就是2月底到5月初，那些日子，胸闷，咳嗽，深痰，喘鸣，鼻涕眼泪加双眼奇痒，简直一个“大喷壶”，目前经过吸入治疗+抗组胺治疗，症状基本控制，但是脑袋还是昏沉沉的。

此外，“本周文献综述”系列会因为订阅的RSS提供的咨询随时更新，因此要注意题目上有没有加入新内容的提示，免得很多重要的信息漏掉了。

本月的《Nature Clinical Practice Cardiovascular Medicine》 （(2008) 5, 22-29）刊登了“章鱼罐综合征（Tako-tsubo syndrome）”，也就是应激性心肌病的继续教育文章——《Stress (Takotsubo) cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning》可全文阅读的。对本病的认识目前还明显不足，不过相信不久它就会和“腹腔间室综合征”一样成为重症医学必须重视的疾病之一。—— 1990年日本的Hikaru Sato教授在日本发现并描述了一个新的综合征，其临床特征包括伴有胸痛的一过性可逆性左心室功能障碍，心电图改变和轻度心肌酶升高类似急性心肌梗死（MI）。心室造影显示，左心室形状类似烧瓶圆底和窄的瓶颈（round bottom and narrow neck）， 形状很像日本用来捕捉墨鱼的瓶子。因此，Sato 教授将之命名为“Tako-tsubo” 心肌病。日文 Tako是墨鱼（Octopus），tsubo是瓶子。近年来，对该综合征有多种命名，包括急性左心室球形改变（acute left ventricular ballooning），可逆性应激性心肌病（reversibe stress cardiomyopathy），破碎心脏综合征（broken heart syndrome）和应激诱发的心肌顿抑（stress induced stunning）。应激确实是发生Tako-tsubo 关键性诱因。患者的经典描述是在症状发生之前即刻有应激性事件，包括情感刺激。激烈运动或精神心理应激。

图示：Schematic representation of the regional differences in response to high catecholamine levels, explaining stress cardiomyopathy

相关文献：《Tako-tsubo综合征研究进展》（中文的）

此外，本月的QJM也发表了《Incidence and clinical significance of left ventricular thrombus in tako-tsubo cardiomyopathy assessed with echocardiography 》（2008 May;101(5):381-6），显然本病的文献量会逐渐增加的。
Background: Left ventricular (LV) thrombus is a known complication of tako-tsubo cardiomyopathy (TC). However, current literature almost exclusively consists of isolated case reports. The aim of this study was to determine the incidence and clinical significance of LV thrombus formation in TC.
Methods and Results: Over a 33-month period 52 patients with TC were assembled into a database at our institution. A retrospective database search was performed to identify patients with LV thrombus among these patients. LV thrombus, by echocardiography, was discovered in four patients[(8%); 95% confidence interval 3–19%]. Thrombus was present at the time of diagnosis in three patients. In one patient thrombus was absent initially and developed later. The LV apex was the site of thrombus formation in two patients, but the true apex was spared in the other two. All four patients had elevated serum levels of C-reactive protein (CRP). Two patients also had thrombocytosis. Treatment with low molecular weight heparin (LMWH) led to resolution of thrombus in all cases.
Conclusions: Our findings suggest that LV thrombus is a noteworthy complication in TC. It can occur both at initial presentation or at anytime later during the disease course. Elevated CRP levels and thrombocytosis may indicate a higher risk of thrombus formation.

Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis
 这是本周最重要的文献，对激素预防与治疗ARDS的疗效进行了荟萃分析。本文之后的引用率可想而知。来自著名的《BMJ》（BMJ. 2008:336:1006-1009） （同样也是免费全文的）。从分析结果来看，激素不可用于ARDS的预防；尽管激素在ARDS起病后用药有降低病死率的趋势，同时在不增加感染并发症的背景下，可增加脱机天数，但是这些只是趋势，激素在ARDS的治疗上到底有没有“决定性”的作用——还是那句老话——我们还需要更多，更大，更强的研究。
Objective To systematically review the efficacy of steroids in the prevention of acute respiratory distress syndrome (ARDS) in critically ill adults, and treatment for established ARDS.
Data sources Search of randomised controlled trials (1966-April 2007) of PubMed, Cochrane central register of controlled trials, Cochrane database of systematic reviews, American College of Physicians Journal Club, health technology assessment database, and database of abstracts of reviews of effects.
Data extraction Two investigators independently assessed trials for inclusion and extracted data into standardised forms; differences were resolved by consensus.
Data synthesis Steroid efficacy was assessed through a Bayesian hierarchical model for comparing the odds of developing ARDS and mortality (both expressed as odds ratio with 95% credible interval) and duration of ventilator free days, assessed as mean difference. Bayesian outcome probabilities were calculated as the probability that the odds ratio would be ≥1 or the probability that the mean difference would be ≥0. Nine randomised trials using variable dose and duration of steroids were identified. Preventive steroids (four studies) were associated with a trend to increase both the odds of patients developing ARDS (odds ratio 1.55, 95% credible interval 0.58 to 4.05; P(odds ratio ≥1)=86.6%), and the risk of mortality in those who subsequently developed ARDS (three studies, odds ratio 1.52, 95% credible interval 0.30 to 5.94; P(odds ratio ≥1)=72.8%). Steroid administration after onset of ARDS (five studies) was associated with a trend towards reduction in mortality (odds ratio 0.62, 95% credible interval 0.23 to 1.26; P(odds ratio ≥1)=6.8%). Steroid therapy increased the number of ventilator free days compared with controls (three studies, mean difference 4.05 days, 95% credible interval 0.22 to 8.71; P(mean difference ≥0)=97.9%). Steroids were not associated with increase in risk of infection.
Conclusions A definitive role of corticosteroids in the treatment of ARDS in adults is not established. A possibility of reduced mortality and increased ventilator free days with steroids started after the onset of ARDS was suggested. Preventive steroids possibly increase the incidence of ARDS in critically ill adults.

A pilot randomized study comparing high and low volume hemofiltration on vasopressor use in septic shock
这也是一篇重要的文献，来自《Intensive care medicine》,并且是提前发表的；对高通量与低通量血滤是否影响感染性休克患者血管活性药物的用量有无影响进行了探讨。结果发现高通量的血滤可减少血管活性药物（加压素）的用量，但是能否带来生存收益还需要更强，更大，更多的研究——怎么全是这个腔，恶！
Objective  High volume hemofiltration (HVHF) has shown potential benefits in septic animals and a few reports suggested a hemodynamic improvement in humans. However, randomized studies are still lacking. Our goal was to evaluate the hemodynamic effects of HVHF in septic shock patients with acute renal failure (ARF).
Design and setting  Prospective randomized study in an intensive care unit (ICU).
Patients  Twenty patients with septic shock and ARF.
Interventions  Patients were randomized to either high volume hemofiltration [HVHF 65 ml/(kg h)] or low volume hemofiltration [LVHF 35 ml/(kg h). Vasopressor dose was adjusted to reach a mean arterial pressure (MAP) > 65 mmHg.
Measurements and results  We performed six hourly measurements of MAP, norepinephrine dose, PaO2/FiO2 and lactate, and four daily urine output and logistic organ dysfunction (LOD) score. Baseline characteristics of the two groups were comparable on randomization. Mean norepinephrine dose decreased more rapidly after 24 h of HVHF treatment compared to LVHF treatment (P = 0.004) whereas lactate and PaO2/FiO2 did not differ between the two treatment groups. During the 4-day follow-up, urine output was slightly increased in the HVHF group (P = 0.059) but the LOD score evolution was not different. Duration of mechanical ventilation, renal replacement therapy and ICU length of stay were also comparable. Survival on day 28 was not affected.
Conclusion  HVHF decreased vasopressor requirement and tended to increase urine output in septic shock patients with renal failure. However, a larger trial is required to confirm our results and perhaps to show a benefit in survival.

The use of hyperventilation therapy after traumatic brain injury in Europe: an analysis of the BrainIT database
过渡通气用于急性创伤性脑外伤的欧洲多中心临床调研。也属于提前发表的。
Objective  To assess the use of hyperventilation and the adherence to Brain Trauma Foundation-Guidelines (BTF-G) after traumatic brain injury (TBI).
Setting  Twenty-two European centers are participating in the BrainIT initiative.
Design  Retrospective analysis of monitoring data.
Patients and participants  One hundred and fifty-one patients with a known time of trauma and at least one recorded arterial blood–gas (ABG) analysis.
Measurements and results  A total number of 7,703 ABGs, representing 2,269 ventilation episodes (VE) were included in the analysis. Related minute-by-minute ICP data were taken from a 30 min time window around each ABG collection. Data are given as mean with standard deviation. (1) Patients without elevated intracranial pressure (ICP) (<20 mmHg) manifested a statistically significant higher PaCO2 (36 ± 5.7 mmHg) in comparison to patients with elevated ICP (≥20 mmHg; PaCO2: 34 ± 5.4 mmHg, P < 0.001). (2) Intensified forced hyperventilation (PaCO2 ≤ 25 mmHg) in the absence of elevated ICP was found in only 49 VE (2%). (3) Early prophylactic hyperventilation (<24 h after TBI; PaCO2 ≤ 35 mmHg, ICP < 20 mmHg) was used in 1,224 VE (54%). (4) During forced hyperventilation (PaCO2 ≤ 30 mmHg), simultaneous monitoring of brain tissue pO2 or SjvO2 was used in only 204 VE (9%).
Conclusion  While overall adherence to current BTF-G seems to be the rule, its recommendations on early prophylactic hyperventilation as well as the use of additional cerebral oxygenation monitoring during forced hyperventilation are not followed in this sample of European TBI centers.

Perioperative anaemia management: consensus statement on the role of intravenous iron
来自《BJA》（2008 May;100(5):599-604.）的文章，有关围术期贫血的静脉补铁的共识建议（我告诉你们一个秘密，我一看这样带有“共识/高峰”之类的标题，第一反应就想到是不是静脉铁剂生产商又在后面push这件事情了。完了，我已经心理障碍了，读者里面有没有心理咨询的，帮我看看，是不是已经属于没事找抽型的了。）不过好在这个多国专家团最后的的结论还算合适——已有的研究均有严重不足，而且总体看来没有发现有什么益处；对于骨科患者如果预计术中或术后有可能出现严重贫血者，可以考虑围术期静脉补铁（但推荐等级很微弱——那就老实点，干脆不推荐得了！），对于其他手术类型者就不要考虑了。—— 不过同志们，事实证明老黄还是比较有水平的，在本文后面列举了专家团的财务冲突声明——专家团首席，第一作者Beris P(Haematology Service, Geneva University Hospital, Geneva, Switzerland)接受了瑞典静脉铁剂生产商Vifor International的劳务费，并主持了该公司赞助的一项临床研究 ;专家团的另外一位来自希腊的Maniatis A(Haematology Division, Henry Dunant Hospital, Athens, Greece) 也接受了丹麦静脉铁剂生产商 Pharmacosmos公司的劳务费。因此，我们有理由想像这类公式会是不是有其他的企图。也因为如此，专家团最后推荐中“需要更大、更强的RCT以证明静脉用铁的有效性和安全性”的“呼吁”就格外值得玩味了。
Beris P.et al.
A multidisciplinary panel of physicians was convened by Network for Advancement of Transfusion Alternatives to review the evidence on the efficacy and safety of i.v. iron administration to increase haemoglobin levels and reduce blood transfusion in patients undergoing surgery, and to develop a consensus statement on perioperative use of i.v. iron as a transfusion alternative. After conducting a systematic literature search to identify the relevant studies, critical evaluation of the evidence was performed and recommendations formulated using the Grades of Recommendation Assessment, Development and Evaluation Working Group methodology. Two randomized controlled trials (RCTs) and six observational studies in orthopaedic and cardiac surgery were evaluated. Overall, there was little benefit found for the use of i.v. iron. At best, i.v. iron supplementation was found to reduce the proportion of patients requiring transfusions and the number of transfused units in observational studies in orthopaedic surgery but not in cardiac surgery. The two RCTs had serious limitations and the six observational limited by the selection of the control groups. Thus, the quality of the available evidence is considered moderate to very low. For patients undergoing orthopaedic surgery and expected to develop severe postoperative anaemia, the panel suggests i.v. iron administration during the perioperative period (weak recommendation based on moderate/low-quality evidence). For all other types of surgery, no evidence-based recommendation can be made. The panel recommends that large, prospective, RCTs be undertaken to evaluate the efficacy and safety of i.v. iron administration in surgical patients. The implementation of some general good practice points is suggested.

Repeat thrombolysis or conservative therapy vs. rescue percutaneous coronary intervention for failed thrombolysis: systematic review and meta-analysis
Testa L,et al.
这不属于老黄的业务，不过《QJM》一直就是我比较喜欢的医学刊物，好久不看，今天想起来翻翻，果然开卷有益。本文是关于急性心梗溶栓失败后“继续溶栓/保守治疗”与“补救性PCI”疗效比较的荟萃分析。因为昨天看到某blog对急性心梗二次溶栓的反思，所以把本文加进来。 
Background: Despite proven advantages of primary percutaneous coronary intervention (PCI), thrombolysis remains the first line treatment for ST-elevation myocardial infarction (STEMI) worldwide. Management of patients with failed thrombolysis is still debated, and data from existing randomized controlled trials are conflicting.
Aim: To compare the risk/benefit profile of repeat thrombolysis (RT) vs. rescue PCI in patients with failed thrombolysis.
Methods: Search of BioMedCentral, CENTRAL, mRCT and PubMed for randomized controlled trials comparing rescue PCI vs. conservative therapy and/or RT vs. conservative therapy. Outcomes of interest assessed by adjusted indirect meta-analysis: major adverse events (MAE, defined as the composite of overall mortality and re-infarction), stroke, congestive heart failure (CHF), major bleeds (MB), and minor bleeds. Overall mortality and re-infarction have been also analysed individually.
Results: Eight trials were included (1318 patients). Follow-up ranged from ‘in-hospital’ to 6 months. No significant difference was found for the risk of MAE [OR 0.93(0.26–3.35), P = 0.4], overall mortality [OR 1.01(0.52–1.95), P = 0.15], stroke [OR 5.03(0.64–39.1), P = 0.58] and CHF [OR 0.74(0.28–1.96), P = 0.6]. Compared with conservative therapy, rescue PCI was associated with a 70% reduction in the risk of re-infarction [OR 0.32(0.14–0.74), P = 0.008], number needed to treat 17. No difference in terms of MB was found [OR 0.5(0.1–2.5), P = 0.09], while a greater risk of minor bleeds was observed with rescue PCI [OR 2.48(1.08–5.7), P = 0.04], number needed to harm 50.
Conclusion: Although the observed benefit is modest, these data support the use of PCI after failed thrombolysis.

2008-05-09

本周我的rss一直没有开，今天早上看了一眼，350条信息！

先说medscape的急症新闻：首先是《Journal of energency medicine》刊登了蛛网膜下腔出血诊疗的最新更新“Aneurysmal Subarachnoid Hemorrhage: Update for Emergency Physicians“(Volume 34, Issue 3, April 2008, Pages 237-251)，在medscape有全文。不过medscape的消息真的比实际出版要慢1个月，上文是4月号刊登的，5月7号medscape才发出消息。又比如American Academy of Allergy, Asthma & Immunology 的2008年会是3月中旬开完的，medscape现在才发布“Highlights of the American Academy of Allergy, Asthma & Immunology 2008 Annual Meeting”显然有点晚了。

实际上5月的《Journal of energency medicine》发表的Serum D-Dimer is a Sensitive Test for the Detection of Acute Aortic Dissection: A Pooled Meta-Analysis （Volume 34, Issue 4, May 2008, Pages 367-376）这一系统评述也很有看头。另外一篇The Medical Management of Acute Coronary Syndromes and Potential Roles for New Antithrombotic Agents(Volume 34, Issue 4, May 2008, Pages 417-428) 也值得关注。

此外，5月9号，MEDSCAPE刊登了最新的评论，就欧洲与美国在各自急性冠脉综合症（ACS）抗凝指南出现不同的推荐意见进行了述评。其实近期欧美指南多次出现同病不同推荐的现象，而且大有愈演愈烈的情况，看来欧洲国家除了在政治上谋求“欧洲的声音”之外，在医学科学上也存在同样地趋势，不过问题是为什么大家都打着“循证”的旗号，却得出不同的结论呢？当然两个指南的发布时间以及引用文献可能存在出入，问题是不论谁先谁后，不都是引用的“询证”的证据吗，难道说这些证据有前后矛盾的结论？最最最关键的是这次的ACS指南又是围绕着的低分子肝素的推荐等级展开的——我们真的需要有潜在利益冲突的专家们的“询证”意见吗—— 国外如此，国内呢？全文引用如下：

Discrepancies in US/European Guidelines on Antithrombotics for ACS
from Heartwire — a professional news service of WebMD

May 9, 2009 – Discrepancies in current recommendations on the use of various antithrombotics in the European and US guidelines for the treatment of acute coronary syndromes is causing confusion, some clinicians have suggested [1].
The editorial, published in the May 10, 2008 issue of the Lancet, is written by Drs John Eikelboom (Hamilton General Hospital, ON), Gordon Guyatt (CLARITY Research Group, Hamilton, ON), and Jack Hirsh (Henderson Research Centre, Hamilton, ON). They say that discrepancies on recommendations regarding enoxaparin and fondaparinux between US and European guidelines undermines confidence in the integrity of guideline development, and they suggest that in the future such discrepancies may be avoided if both committees met and debated differences between their recommendations and if they included nonconflicted methodologists to ensure that criteria for evidence quality were applied consistently.
They write: "The disagreements in the recommendations for enoxaparin and fondaparinux seem to stem from differences in both the interpretation of the trial data and from differences in the application of nearly identical criteria that were used by both committees to classify the evidence. Without an opportunity to review the reasoning behind each recommendation, it is difficult for readers to decide which recommendations to follow."
Eikelboom et al note that the American College of Cardiology (ACC)/American Heart Association (AHA) and the European Society of Cardiology (ESC) both updated their ACS guidelines last year [2,3]. "The committees reviewed the same research and used nearly identical criteria to rate the strength of the recommendations and to grade the quality of the evidence, but they interpreted the evidence for acute anticoagulant use differently and so reached different conclusions. Therefore, physicians who read recommendations from both the US and European societies might be confused."
They point out that the ACC/AHA gave enoxaparin and fondaparinux a class 1 rating for conservatively and invasively managed patients, implying that there is evidence or general agreement that the treatments are useful or effective. By contrast, the ESC gave enoxaparin a class 2 rating for conservatively and invasively managed patients, implying that there is conflicting evidence or divergence of opinion about the usefulness of enoxaparin, and did not recommend fondaparinux for patients undergoing urgent invasive procedures. "For clinicians, this is the most important area of disagreement between the guidelines, because it directly affects the choice of anticoagulant; unfortunately, it is also the hardest to explain," the authors state.
They suggest that the ACC/AHA must have placed greater weight than the ESC on the results of a meta-analysis that showed that enoxaparin compared with heparin reduced MI and did not increase bleeding. In contrast, the ESC seemed to place greater weight on the results of the SYNERGY trial (which showed that enoxaparin was as effective as heparin but was associated with more bleeding in invasively treated patients) and the OASIS-5 trial (which found that enoxaparin was as effective as fondaparinux but caused more bleeding and was associated with excess strokes and deaths at day 30).
Eikelboom et al note that the divergent recommendations for fondaparinux probably also reflect differences in the interpretation of the OASIS-5 trial, which showed an excess of catheter thrombosis in patients treated with fondaparinux undergoing PCI. This, they suggest, led the ESC not to recommend fondaparinux in invasively managed patients, "but the strong recommendation by the ACC/AHA for fondaparinux in invasively managed patients implies that they did not think the risk of catheter thrombosis to be an important issue, provided that a bolus dose of heparin is used at the time of the invasive procedure."
Clarifying the US Position
Chair of the AHC/AHA guidelines committee, Dr Jeffery Anderson (University of Utah, Salt Lake City), told heartwire that the Lancet editorial had somewhat misread the recommendations. He pointed out that although the ESC doesn't recommend fondaparinux for patients getting urgent revascularization, it has given the drug a 1A recommendation for delayed invasive therapy within three days. He added that the ACC/AHA recommendation for fondaparinux was for an invasive strategy within 48 hours, not an urgent strategy, and gives it a 1B, not a 1A, and it also specifies giving it with heparin.
"Thus, one could interpret the ACC/AHA guideline as being more conservative, not more liberal, for fondaparinux. The difference is the way 'early invasive' is defined. Reading the text carefully reveals similar concerns about catheter thrombosis by both societies, and neither advances fondaparinux particularly for invasive patients. So the editorial obviously doesn't fairly assess the very close overall agreement in the sense of both guidelines that is included in the text. However, OASIS-5 was a very large and well-done study that indicates fondaparinux as being successful for the overall efficacy and safety end points, regardless of strategy, despite the small excess of catheter thrombosis," Anderson commented.
Different Focuses on Benefit/Risk?
Dr Sanjay Kaul (Cedar Sinai Medical Center, Los Angeles) suggests that one reason for the discordant recommendations between the ACC/AHA and ESC guidelines is that the benefit/risk trade-off focuses only on efficacy outcomes in US guidelines but on both efficacy and safety in the European guidelines. "Thus, while enoxaparin gets a class 1A recommendation in the ACC/AHA guidelines (based only on equivalent efficacy with heparin), it is downgraded in the ESC guidelines (based on both equivalent efficacy but increased bleeding compared with heparin or fondaparinux)," he commented to heartwire.
"Ideally, guidelines must be written in a manner that communicates a clear, rational, and practical balance between clinically important magnitude of benefits and harms, not just statistically significant benefits," Kaul said. He adds: "Rigorous standardized analytical methodology that focuses on benefit/risk (and cost) assessment might also improve the quality of adjudication of evidence in guideline development."
In a recent discussion on theheart.org on differences between the US and European guidelines (sponsored by Sanofi-Aventis and Bristol-Myers Squibb), speakers noted that although enoxaparin and fondaparinux were not given such strong recommendations in the European guidelines, they were both used more extensively in Europe than they were in the US [4].
Dr Keith Fox (University of Edinburg, Scotland) said that fondaparinux was favored by some clinicians in the UK because it showed a mortality advantage over enoxaparin in OASIS-5; as it is not sufficient to be used alone in the cath lab, many centers use unfractionated heparin in the cath lab if patients have been pretreated with fondaparinux. But enoxaparin was still the most widely used agent in his center, Fox added.
Dr Charles Pollack (University of Pennsylvania School of Medicine, Philadelphia) said he was happy to use either enoxaparin or unfractionated heparin, both of which have class 1A recommendations in the US. He pointed out that there was very little use of fondaparinux in the US at present, probably because it was not yet approved for the ACS indication there. "Fondaparinux is attractive, but there is very little experience of this drug in the US, and we don't like the idea of having to give extra unfractionated heparin on top of it in the lab," he said.
Dr Giles Montalescot (Hospital La Pitie Salpetriere, Paris, France) concurred in this point. "We have moved away from using unfractionated heparin, and we put almost everyone on enoxaparin, as it covers all situations. If we use fondaparinux, we would have to bring back unfractionated heparin, but we don't use it anymore," he said. He added that his center does use fondaparinux in patients who it is known will not be going to the cath lab.
On the other option of bivalirudin, Pollack noted that it was not used much in the US to treat ACS patients and had not been approved yet for use outside the cath lab, although there were signs that it was now starting to move into the upstream setting.
Eikelboom has received honoraria from and has worked on studies with GlaxoSmithKline, Sanofi-Aventis, and the Medicines Company. Hirsh has received an honorarium from GlaxoSmithKline for attending an advisory meeting.
   1. Eikelboom J, Guyatt G and Hirsh J. Guidelines for anticoagulant use in acute coronary syndromes. Lancet 2008; 371: 1559-1561.
   2. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2007; 50: e1–157. Abstract
   3. Bassand JP, Hamm CW, Ardissino D, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: the task force for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes of the European Society of Cardiology. Eur Heart J 2007; 28: 1598–1660. Abstract
   4. Lost in translation: US and European guidelines for the pharmacologic management of ACS. theheart.org. [CME programs > Clinical cardiology]; April 10, 2008. Available at http://www.theheart.org/article/846579.do.

IntroductionAnimal studies of acute lung injury (ALI) suggest nebulised heparin may limit damage from fibrin deposition in the alveolar space and microcirculation. To date no human studies have been undertaken. We assessed the feasibility, safety and potential anti-coagulant effects of administration of nebulised heparin to patients with ALI. Methods: An open label phase 1 trial of 4 escalating doses of nebulised heparin. A total of 16 ventilated patients with ALI were studied. The first group was administered a total of 50,000 U/day, the second 100,000 U/day, the third 200,000 U/day and the fourth 400,000 U/day. Assessments of lung function included the arterial to inspired oxygen ratio (PaO2/FiO2), lung compliance and the alveolar dead space fraction. Monitoring of anti-coagulation included the activated partial thromboplastin time (APTT) and the thrombin clotting time (TCT). Bronchoalveolar lavage (BAL) fluid was collected and prothrombin fragment (PTF) and tissue plasminogen activator (t-PA) levels were assessed. Analysis of variance was used to compare the effects of dose. Results: No serious adverse events occurred for any dose. The changes over time for the PaO2/FiO2, lung compliance and the alveolar dead space fraction levels were similar for all doses. A trend to increased APTT and TCT levels was present with higher doses (p = 0.09 and 0.1, respectively). For the highest dose the APTT reached 64 seconds and following cessation of nebulised heparin fell to 39 seconds (p = 0.06). In BAL samples a trend to reduced PTF levels was present with higher doses (p = 0.1), while t-PA levels were similar for all doses. Conclusions: Administration of nebulised heparin to mechanically ventilated patients with ALI is feasible. It was not associated with any serious adverse events and at higher doses increased APTT levels. Larger trials are required to further investigate the safety and efficacy of nebulised heparin. In these trials due consideration must be given to systemic anti-coagulant effects. Trial registration: Australian Clinical trials registry ACTRN12606000388516
本期的《current opinion in critical care 》是关于心肺复苏和心肺监测（实际没有呼吸力学监测，只是血液动力学相关指标以及内皮细胞功能监测），不写了，挂张图得了。