先说肺栓塞，本周的MEDSCAP看刊登了转自《Seminars in Respiratory and Critical Care Medicine》一篇《Massive Pulmonary Embolism: What Level of Aggression?》，作者是来自德国哥庭根大学的Stavros V. Konstantinides。《Seminars in Respiratory and Critical Care Medicine》来自Thime公司，应该也属于sciencedirect，不过可能独立运营，经营的一些杂志也很不错，看来我的rss又可以加新了。这次的medscape引用的这篇文献其实是该杂志2008年第一卷《Deep Venous Thrombosis and Pulmonary Thromboembolism: Evolving Concepts and Controversies 》专刊（也就是深静脉血栓）的，2008年第二卷是关于真菌感染专刊的。本文的要目是：
ABSTRACT
RESOLVED AND UNRESOLVED ISSUES IN THE MANAGMENT OF ACUTE PULMONARY EMBOLISM
THROMBOLYSIS: BENEFITS, RISKS, AND UNCERTAINTIES
AGGRESSIVE THROMBOLYTIC TREATMENT FOR UNSTABLE PATIENTS WITH MASSIVE PULMONARY EMBOLISM
NORMOTENSIVE PATIENTS WITH NONMASSIVE PULMONARY EMBOLISM: THE RATIONALE FOR RISK STRATIFICATION
RISK STRATIFICATION OF NORMOTENSIVE PATIENTS WITH PULMONARY EMBOLISM: IMAGING OF THE RIGHT VENTRICLE
ADDITIONAL TOOLS FOR RISK ASSESMENT: CARDIAC BIOMARKERS
IS SUBMASSIVE PULMONARY EMBOLISM AN INDICATION FOR THROMBOLYTIC TREATMENT?
CONCLUSION
REFERENCES
从章节的题目看起来，还不错，讨论了目前肺栓塞溶栓治疗的现状，值得一看。
这一期专刊的详细目录专刊因为是专刊性质，因此每篇文章就像综述一样。下面是本期的目录，看了一下，没有特大腕，只有大腕，但是内容非常好，仅从题目看就很吸引人，很值得推荐：
PREFACE
Tapson, Victor F.:
Deep Venous Thrombosis and Pulmonary Thromboembolism: Evolving Concepts and Controversies
Moores, Lisa K.; Holley, Aaron B.:
Computed Tomography Pulmonary Angiography and Venography: Diagnostic and Prognostic Properties
Hargett, C. William; Tapson, Victor F.:
Clinical Probability and D-dimer Testing: How Should We Use Them in Clinical Practice?
Whitlatch, Nicole L.; ortel, Thomas L.:
Thrombophilias: When Should We Test and How Does It Help?
Garcia, David A.; Spyropoulos, Alex C.:
Update in the Treatment of Venous Thromboembolism
Konstantinides, Stavros V.:
Massive Pulmonary Embolism: What Level of Aggression?
Vedantham, Suresh:
Interventional Approaches to Acute Venous Thromboembolism
Linkins, Lori-Ann; Warkentin, Theodore E.:
The Approach to Heparin-Induced Thrombocytopenia
Yavin, Yshai; Cohen, Alexander T.:
Venous Thromboembolism Prophylaxis for the Medical Patient: Where Do We Stand?
Petralia, Gloria A.; Kakkar, Ajay K.:
Venous Thromboembolism Prophylaxis for the General Surgical Patient: Where Do We Stand?
Hoppensteadt, Debra A.; Jeske, Walter; Walenga, Jeanine; Fareed, Jawed; Hemostasis and Thrombosis Research Laboratories Loyola University Chicago:
The Future of Anticoagulation
......

本周的《JAMA》一篇的《Improvement in Process of Care and Outcome After a Multicenter Severe Sepsis Educational Program in Spain》(AMA. 2008;299(19):2294-2303.)的西班牙“edusepsis项目”值得一看:
Context  Concern exists that current guidelines for care of patients with severe sepsis and septic shock are followed variably, possibly due to a lack of adequate education.
Objective  To determine whether a national educational program based on the Surviving Sepsis Campaign guidelines affected processes of care and hospital mortality for severe sepsis.
Design, Setting, and Patients  Before and after design in 59 medical-surgical intensive care units (ICUs) located throughout Spain. All ICU patients were screened daily and enrolled if they fulfilled severe sepsis or septic shock criteria. A total of 854 patients were enrolled in the preintervention period (November-December 2005), 1465 patients during the postintervention period (March-June 2006), and 247 patients during the long-term follow-up period 1 year later (November-December 2006) in a subset of 23 ICUs.
Intervention  The educational program consisted of training physicians and nursing staff from the emergency department, wards, and ICU in the definition, recognition, and treatment of severe sepsis and septic shock as outlined in the guidelines. Treatment was organized in 2 bundles: a resuscitation bundle (6 tasks to begin immediately and be accomplished within 6 hours) and a management bundle (4 tasks to be completed within 24 hours).
Main Outcome Measures  Hospital mortality, differences in adherence to the bundles' process-of-care variables, ICU mortality, 28-day mortality, hospital length of stay, and ICU length of stay.
Results  Patients included before and after the intervention were similar in terms of age, sex, and Acute Physiology and Chronic Health Evaluation II score. At baseline, only 3 process-of-care measurements (blood cultures before antibiotics, early administration of broad-spectrum antibiotics, and mechanical ventilation with adequate inspiratory plateau pressure) we had compliance rates higher than 50%. Patients in the postintervention cohort had a lower risk of hospital mortality (44.0% vs 39.7%; P = .04). The compliance with process-of-care variables also improved after the intervention in the sepsis resuscitation bundle (5.3% [95% confidence interval [CI], 4%-7%] vs 10.0% [95% CI, 8%-12%]; P < .001) and in the sepsis management bundle (10.9% [95% CI, 9%-13%] vs 15.7% [95% CI, 14%-18%]; P = .001). Hospital length of stay and ICU length of stay did not change after the intervention. During long-term follow-up, compliance with the sepsis resuscitation bundle returned to baseline but compliance with the sepsis management bundle and mortality remained stable with respect to the postintervention period.
Conclusions  A national educational effort to promote bundles of care for severe sepsis and septic shock was associated with improved guideline compliance and lower hospital mortality. However, compliance rates were still low, and the improvement in the resuscitation bundle lapsed by 1 year.
看来所谓的sepsis集束化治疗截至目前最大型的研究已经出炉了，而且获得了阳性结论，如果我们再看医生护士极低的顺应性就应该预见到如果提高顺应性，可能病死率会更为显著的减少—— 但是我对这种简单的“说教运动”就能改善病死率的做法表示怀疑——在文后的述评中对此也有评论。
为此，刊发了波士顿大学Jeremy M. Kahn,等人的述评——《Improving Sepsis Care  The Road Ahead》（JAMA. 2008;299(19):2322-2323.），主要内容如下：
In recent years there have been unprecedented advances in the understanding of the epidemiology, pathophysiology, and treatment of sepsis syndrome.1-3 This work has culminated in several clinical trials demonstrating the efficacy of targeted interventions to improve sepsis-related outcomes.4-6 These interventions include not only novel therapeutic agents such as drotrecogin alfa but also treatments directed at improving the way more traditional therapy is delivered, such as early resuscitation and low-tidal volume ventilation for acute lung injury.4-6
Unfortunately the gaps between evidence and practice have long been huge.7 Indeed, most available data suggest that clinical trial and observational study results have not yet changed clinical practice in sepsis care. Few emergency departments have implemented protocols for early resuscitation of patients with severe sepsis, delayed and inappropriate antibiotic administration remains common, and many patients with acute lung injury receive mechanical ventilation with potentially injurious tidal volumes.8-10
Numerous obstacles get in the way of implementing clinical evidence. Clinicians may be unaware of published evidence, disagree with practice guidelines, or be unable to effect change due to environmental and structural barriers.11 These challenges are particularly salient in sepsis care, which requires dedicated efforts between multiple disciplines and coordination of care throughout the hospital, all in a setting in which time to treatment is central. Comprehensive strategies are needed to standardize practice, improve care processes, and optimize outcomes for this high-risk patient group.
Recent evidence suggests that grouping care practices together into "bundles" may be an effective method to improve outcomes for complex diseases such as catheter-related bloodstream infections, ventilator-associated pneumonia, and even sepsis.12-14 But it has proved extremely challenging to take complex care improvement programs and disseminate them broadly across a region, state, country, or across national boundaries.
In this issue of JAMA, Ferrer and colleagues15 report the findings of an ambitious, nationwide effort to improve the quality of care for patients with severe sepsis and septic shock. ..... Improvement in survival was greatest in hospitals with the poorest baseline performance. These performance gains provide an important process-outcome link in support of the sepsis guidelines because some of the elements of this campaign have not yet been strongly linked to outcome in patients with severe sepsis.
The intervention was associated with important process and outcome improvements even though it was relatively simple. Didactic teaching and passive guideline dissemination are not the most effective methods of behavior change.17 The investigators did not include some of the more effective methods for implementing evidence-based practice, including academic detailing, computerized reminders, and repeated audit and feedback.18-19 Additionally, the intervention was homogeneous across sites, with no attempt to customize the program based on local cultures or specific organizational barriers.20 The fact that performance improved even after this type of intervention is probably due to poor compliance and high mortality at baseline.
The study has limitations. Most notably, the absence of a cluster randomized design or even concurrent controls leaves open the possibility that temporal trends or changes in case-mix led to the observed association. Nonetheless, the sheer scope and scale of this initiative should not be discounted. The campaign in Spain represents the culmination of a multi-year effort involving coordination between the investigators, the Spanish Society of Intensive Care Medicine and Coronary Care Units, and the participating sites. Simply the fact that a national professional society undertook a project to improve its country's health and was able to achieve improvements in both process and outcome makes this work unlike any previous quality-improvement initiative in hospital medicine. Perhaps the greatest lesson of this study is that through multicenter collaboration it is possible to meaningfully effect change in the quality of hospital care, not just locally but across an entire nation.
This work also highlights several of the challenges in hospital-based quality improvement. First, only a minority of Spanish hospitals were willing to participate in the program, and several dropped out. Hospitals were not asked to justify their nonparticipation, but many likely either could not identify a local champion or were unwilling to devote scarce resources for a collaborative quality-improvement effort. Innovative methods of quality improvement that do not require local champions and are more easily exportable to multiple sites, perhaps involving use of information technology, may be more effective.
Second, baseline performance was relatively poor despite the presence of 24-hour intensivist staffing at all sites. Intensivist physician staffing is consistently linked to improvements in the process and outcome of critical care.21-22 Yet it is clear that intensivists alone are not a cure for poor quality. Aggressive quality-improvement efforts are needed even in optimally staffed ICUs.
Third, the increases in guideline adherence were modest, with some process measures increasing by only a few percentage points. Even after the intervention, performance on many measures was far below what would be considered ideal. Nor were all improvements sustained in a subset of hospitals that measured process and outcome for a year after the intervention; many measures returned to baseline rates. The benefits of this type of intervention might well increase over time if organizations develop effective ways to ensure that the bundles are implemented, but might also wane if the focus shifts to other areas. Future research should address how to better maintain process improvements, including the role of incentives and ongoing performance measurement.
Ferrer and colleagues supply powerful evidence that broad-based quality improvement in sepsis care is feasible on a national scale. The data also suggest that delivering a bundle of care effectively for patients with sepsis may be as or even more important than developing new therapies. Indeed, the absolute risk reduction in hospital mortality observed in this study would translate to an impressive number of lives saved if this type of intervention were successfully implemented on an international scale. The science of quality improvement must include not only development of effective measures, but also evaluation of what techniques for spreading and maintaining them are most effective.
Furthermore, this study should be a wake-up call to policy makers, a challenge to the leaders of professional societies, and a road map for the path ahead. No longer is it acceptable to simply publish practice guidelines and hope that quality improvement happens at the local level. Development of these guidelines should be followed by rigorous testing, and, when results are positive, by dedicated regional, national, and even international implementation efforts. Such broad-based efforts are needed to achieve population-level benefits from interventions known to be effective.
REFERENCES
1. Abraham E, Singer M. Mechanisms of sepsis-induced organ dysfunction. Crit Care Med. 2007;35(10):2408-2416.
2. Wheeler AP. Recent developments in the diagnosis and management of severe sepsis. Chest.2007;132(6):1967-1976.
3. Angus DC, Linde-Zwirble WT, Lidicker J; et al. Epidemiology of severe sepsis in the United States. Crit Care Med. 2001;29(7):1303-1310.
4. Bernard GR, Vincent JL, Laterre PF; et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344(10):699-709.
5. Rivers E, Nguyen B, Havstad S; et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-1377.
6. Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301-1308.
7. Lomas J, Sisk JE, Stocking B. From evidence to practice in the United States, the United Kingdom, and Canada. Milbank Q. 1993;71(3):405-410
8. Carlbom DJ, Rubenfeld GD. Barriers to implementing protocol-based sepsis resuscitation in the emergency department. Crit Care Med. 2007;35(11):2525-2532.
9. Esteban A, Ferguson ND, Meade MO; et al. Evolution of mechanical ventilation in response to clinical research. Am J Respir Crit Care Med. 2008;177(2):170-177.
10. De Miguel-Yanes JM, Andueza-Lillo JA, Gonzalez-Ramallo VJ; et al. Failure to implement evidence-based clinical guidelines for sepsis at the ED. Am J Emerg Med. 2006;24(5):553-559.
11. Cabana MD, Rand CS, Powe NR; et al. Why don't physicians follow clinical practice guidelines? a framework for improvement. JAMA. 1999;282(15):1458-1465
12. Resar R, Pronovost P, Haraden C; et al. Using a bundle approach to improve ventilator care processes and reduce ventilator-associated pneumonia. Jt Comm J Qual Patient Saf. 2005;31(5):243-248.
13. Nguyen HB, Corbett SW, Steele R; et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med. 2007;35(4):1105-1112.
14. Pronovost P, Needham D, Berenholtz S; et al. An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med. 2006;355(26):2725-2732.
15. Ferrer R, Artigas A, Levy MM; et al, for the Edusepsis Study Group. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA. 2008;299(19):2294-2303.
16. Dellinger RP, Levy MM, Carlet JM; et al. Surviving Sepsis Campaign. Crit Care Med. 2008;36(1):296-327.
17. Grimshaw JM, Shirran L, Thomas R; et al. Changing provider behavior. Med Care. 2001;39(8)(suppl 2):II2-II45.
18. Soumerai SB, McLaughlin TJ, Avorn J. Improving drug prescribing in primary care. Milbank Q. 1989;67(2):268-317
19. Bates DW, Kuperman GJ, Wang S; et al. Ten commandments for effective clinical decision support. J Am Med Inform Assoc. 2003;10(6):523-530.
20. Curtis JR, Cook DJ, Wall RJ; et al. Intensive care unit quality improvement. Crit Care Med. 2006;34(1):211-218.
21. Pronovost PJ, Angus DC, Dorman T, Robinson KA, Dremsizov TT, Young TL. Physician staffing patterns and clinical outcomes in critically ill patients: a systematic review. JAMA. 2002;288(17):2151-2162. FREE FULL TEXT
22. Kahn JM, Brake H, Steinberg KP. Intensivist physician staffing and the process of care in academic medical centres. Qual Saf Health Care. 2007;16(5):329-333.

本周另外一篇重要的文献是血液替代品造成心梗以及死亡风险的荟萃分析——《Cell-Free Hemoglobin-Based Blood Substitutes and Risk of Myocardial Infarction and Death》（JAMA. 2008;299(19):2304-2312.）
Context  Hemoglobin-based blood substitutes (HBBSs) are infusible oxygen-carrying liquids that have long shelf lives, have no need for refrigeration or cross-matching, and are ideal for treating hemorrhagic shock in remote settings. Some trials of HBBSs during the last decade have reported increased risks without clinical benefit.
Objective  To assess the safety of HBBSs in surgical, stroke, and trauma patients.
Data Sources  PubMed, EMBASE, and Cochrane Library searches for articles using hemoglobin and blood substitutes from 1980 through March 25, 2008; reviews of Food and Drug Administration (FDA) advisory committee meeting materials; and Internet searches for company press releases.
Study Selection  Randomized controlled trials including patients aged 19 years and older receiving HBBSs therapeutically. The database searches yielded 70 trials of which 13 met these criteria; in addition, data from 2 other trials were reported in 2 press releases, and additional data were included in 1 relevant FDA review.
Data Extraction  Data on death and myocardial infarction (MI) as outcome variables.
Results  Sixteen trials involving 5 different products and 3711 patients in varied patient populations were identified. A test for heterogeneity of the results of these trials was not significant for either mortality or MI (for both, I2 = 0%, P ≥ .60), and data were combined using a fixed-effects model. Overall, there was a statistically significant increase in the risk of death (164 deaths in the HBBS-treated groups and 123 deaths in the control groups; relative risk [RR], 1.30; 95% confidence interval [CI], 1.05-1.61) and risk of MI (59 MIs in the HBBS-treated groups and 16 MIs in the control groups; RR, 2.71; 95% CI, 1.67-4.40) with these HBBSs. Subgroup analysis of these trials indicated the increased risk was not restricted to a particular HBBS or clinical indication.
Conclusion  Based on the available data, use of HBBSs is associated with a significantly increased risk of death and MI.

本周的《NEJM》最重要的文章就是the VA/NIH Acute Renal Failure Trial Network发表的《Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury》。也就是危重症肾脏替代治疗的比较研究 ——本文对所谓的强化肾脏替代治疗与非强化肾脏替代治疗进行了比较。所谓的强化与非强化肾脏替代治疗按照作者的定义是：In the group receiving the intensive-therapy strategy, intermittent hemodialysis and sustained low-efficiency dialysis were provided six times per week (every day except Sunday), and continuous venovenous hemodiafiltration was prescribed to provide a flow rate of the total effluent (the sum of the dialysate and ultrafiltrate) of 35 ml per kilogram of body weight per hour, based on the weight before the onset of acute illness. In the less-intensive strategy, intermittent hemodialysis and sustained low-efficiency dialysis were provided three times per week (on alternate days except Sunday), and continuous venovenous hemodiafiltration was prescribed to provide a total effluent flow rate of 20 ml per kilogram per hour. 主要的区别就是大流量血滤（强化组 35 ml per kilogram of body weight per hour）与小流量血滤（ 20 ml per kilogram per hour）以及透析次数的区别。结果发现强化治疗与非强化治疗在病死率，肾功能改善或者脏器衰竭评分等各方面都没有差异！！
Background The optimal intensity of renal-replacement therapy in critically ill patients with acute kidney injury is controversial.
Methods We randomly assigned critically ill patients with acute kidney injury and failure of at least one nonrenal organ or sepsis to receive intensive or less intensive renal-replacement therapy. The primary end point was death from any cause by day 60. In both study groups, hemodynamically stable patients underwent intermittent hemodialysis, and hemodynamically unstable patients underwent continuous venovenous hemodiafiltration or sustained low-efficiency dialysis. Patients receiving the intensive treatment strategy underwent intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml per kilogram of body weight per hour; for patients receiving the less-intensive treatment strategy, the corresponding treatments were provided thrice weekly and at 20 ml per kilogram per hour.
Results Baseline characteristics of the 1124 patients in the two groups were similar. The rate of death from any cause by day 60 was 53.6% with intensive therapy and 51.5% with less-intensive therapy (odds ratio, 1.09; 95% confidence interval, 0.86 to 1.40; P=0.47). There was no significant difference between the two groups in the duration of renal-replacement therapy or the rate of recovery of kidney function or nonrenal organ failure. Hypotension during intermittent dialysis occurred in more patients randomly assigned to receive intensive therapy, although the frequency of hemodialysis sessions complicated by hypotension was similar in the two groups.
Conclusions Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour.
建议大家看一看本文的述评《Dialysis in Acute Kidney Injury — More Is Not Better》(Joseph V. Bonventre, M.D., Ph.D.)

New Fever in Critically Ill Patients ^{New! 重症患者发热指南}

"Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America"

Crit Care Med 2008 Vol. 36, No. 4 这是IDSA( Infectious Disease Society of America )继《Clinical Infectious Diseases》1998年发表成人重症患者发热指南后的最新更新，是和美国危重病协会（SCCM）联合发表，因此转移到《Critical care medicine》发表。我这里给的链接是从IDSA看到的。

本周的《Lancet》刊登了中国中山医科大学主持的多中心的早期强化胰岛素对于初诊2型糖尿病的疗效观察研究，这项前瞻性的病例对照研究作为本周《Lancet》的封面报道，看来意义非凡。
Background
Early intensive insulin therapy in patients with newly diagnosed type 2 diabetes might improve β-cell function and result in extended glycaemic remissions. We did a multicentre, randomised trial to compare the effects of transient intensive insulin therapy (continuous subcutaneous insulin infusion [CSII] or multiple daily insulin injections [MDI]) with oral hypoglycaemic agents on β-cell function and diabetes remission rate.
Methods
382 patients, aged 25–70 years, were enrolled from nine centres in China between September, 2004, and October, 2006. The patients, with fasting plasma glucose of 7·0–16·7 mmol/L, were randomly assigned to therapy with insulin (CSII or MDI) or oral hypoglycaemic agents for initial rapid correction of hyperglycaemia. Treatment was stopped after normoglycaemia was maintained for 2 weeks. Patients were then followed-up on diet and exercise alone. Intravenous glucose tolerance tests were done and blood glucose, insulin, and proinsulin were measured before and after therapy withdrawal and at 1-year follow-up. Primary endpoint was time of glycaemic remission and remission rate at 1 year after short-term intensive therapy. Analysis was per protocol. This study was registered with ClinicalTrials.gov, number NCT00147836.
Findings
More patients achieved target glycaemic control in the insulin groups (97·1% [133 of 137] in CSII and 95·2% [118 of 124] in MDI) in less time (4·0 days [SD 2·5] in CSII and 5·6 days [SD 3·8] in MDI) than those treated with oral hypoglycaemic agents (83·5% [101 of 121] and 9·3 days [SD 5·3]). Remission rates after 1 year were significantly higher in the insulin groups (51·1% in CSII and 44·9% in MDI) than in the oral hypoglycaemic agents group (26·7%; p=0.0012). β-cell function represented by HOMA B and acute insulin response improved significantly after intensive interventions. The increase in acute insulin response was sustained in the insulin groups but significantly declined in the oral hypoglycaemic agents group at 1 year in all patients in the remission group.
Interpretation
Early intensive insulin therapy in patients with newly diagnosed type 2 diabetes has favourable outcomes on recovery and maintenance of β-cell function and protracted glycaemic remission compared with treatment with oral hypoglycaemic agents.
Funding
973 Programme from the Chinese Government, the Natural Science Foundation of Guangdong Province Government, Novo Nordisk (China), and Roche Diagnostics (Shanghai).
Affiliations
a. Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
b. First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
c. Affiliated Hospital of Guiyang Medical College, Guizhou, China
d. Gulou Hospital of Nanjing University, Nanjing, China
e. Xiangya Second Affiliated Hospital of Central South University, Changsha, China
f. West China Hospital of Sichuan University, Chengdu, China
g. First Affiliated Hospital of Guangxi Medical University, Nanning, China
h. Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
i. First Affiliated Hospital of Fujian Medical University, Fuzhou, China
Correspondence to: Professor Jianping Weng, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China, 510630

本月，也就是6月号的《Anesthesia & Analgesia 》主要的课题之一就是在“儿科麻醉”栏目中对麻醉是否影响儿童脑/神经系统发育进行了综合报道，既有正面意见又有反面意见。这个栏目中另外一篇综述值得推荐—— Neuroprotective Strategies for the Neonatal Brain (Review Article，Anesth Analg 2008 106: 1670-1680. 【IMPLICATIONS: Injury to the perinatal brain is a leading cause of death and disability in children. Understanding the pathophysiology of perinatal brain damage will help to identify potential targets for neuroprotective strategies.】 也就是新生儿的神经保护策略。在《Anesthesia & Analgesia 》的“危重病与创伤”栏目下，有三篇文献，分别是：
1. Peripheral Blood Hematocrit in Critically Ill Surgical Patients: An Imprecise Surrogate of True Red Blood Cell Volume
Anesth Analg 2008 106: 1808-1812.  
IMPLICATIONS: The peripheral blood hematocrit assayed in the clinical laboratory may not provide an accurate estimate of red blood cell volume in critically ill surgical patients. Measurement of plasma volume and red blood cell volume may provide a more accurate guide for blood transfusion requirements.
2. Free Cortisol in Sepsis and Septic Shock
Anesth Analg 2008 106: 1813-1819. 
IMPLICATIONS: Calculated free cortisol concentrations correlate well with total cortisol concentration, and free cortisol calculation does not predict unfavorable outcome better than total cortisol levels. Clinically, calculation of free cortisol does not help to identify patients who would benefit from corticoid treatment in severe sepsis and septic shock.
3. Vascular Endothelial Growth Factor in Severe Sepsis and Septic Shock
Anesth Analg 2008 106: 1820-1826. 
IMPLICATIONS: Serum vascular endothelial growth factor (VEGF) concentrations are increased in patients with severe sepsis. Although nonsurvivors have significantly lower levels than patients with better outcome, VEGF concentrations do not predict hospital mortality.
3篇文献发的共同点就是其所报道的指标——外周血红细胞压积、游离皮质醇以及血清内皮生长因子都不能用于有效评估病情或者用于预后评估；后两篇文献都是芬兰“Finnsepsis Study Group”的研究报告。

        梭状芽胞杆菌为革兰阳性厌氧杆菌，以产气荚膜杆菌（魏氏杆菌）、水肿杆菌和腐败杆菌为主要，其次为产芽胞杆菌和溶组织杆菌等，临床上见到的气性坏疽，常是两种以上致病菌的混合感染。  

梭状芽胞杆菌广泛存在于泥土和人畜粪便中，所以易进入伤口，但并不一定致病。气性坏疽的发生，并不单纯地决定于气性坏疽杆菌的存在，而更决定于人体抵抗力和伤口的情况，即需要一个利于气性坏疽杆菌生长繁殖的缺氧环境。因此，失水、大量失血或休克，而又有伤口大片组织坏死、深层肌肉损毁，尤其是大腿和臀部损伤，弹片存留、开放性骨折或伴有主要血管损伤，使用止血带时间过长等情况，容易发生气性坏疽。  

气性坏疽的病原菌主要在伤口内生长繁殖，很少侵入血液循环引起败血症。产气夹膜杆菌产生α毒素、胶原酶、透明质酸酶、溶纤维酶和脱氧核糖核酸酶等，红细胞破坏引起溶血、血红蛋白尿、尿少、肾组织坏死、水肿、液化，肌肉大片坏死，使病变迅速扩散、恶化。糖类分解产生大量气体，使组织膨胀；蛋白质的分解和明胶的液化，产生硫化氢，使伤口发生恶臭。由于局部缺血，血浆渗出，及各种毒素的作用，伤口内的组织和肌肉，进一步坏死和腐化，更利于细菌的繁殖，使病变更为恶化。大量的组织坏死和外毒素的吸收，可引起严重的毒血症。某些毒素可直接侵犯心、肝和肾，造成局灶性坏死，引起这些器官的功能减退。

潜伏期可短至6～8h，但一般为1～4天。  

局部表现 病人自觉患部沉重，有包扎过紧感。以后，突然出现患部“胀裂样”剧痛，不能用一般止痛剂缓解。患部肿胀明显，压痛剧烈。伤口周围皮肤水肿、紧张，苍白、发亮，很快变为紫红色，进而变为紫黑色，并出现大小不等的水泡。伤口内肌肉由于坏死，呈暗红色或土灰色，失去弹性，刀割时不收缩，也不出血，犹如煮熟的肉。伤口周围常扪到捻发音，表示组织间有气体存在。轻轻挤压患部，常有气泡从伤口逸出，并有稀薄、恶臭的浆液样血性分泌物流出。

全身症状 早期病人表情淡漠，有头晕、头痛、恶心、呕吐、出冷汗、烦躁不安、高热、脉搏快速（100～120次/min），呼吸迫促，并有进行性贫血。晚期有严重中毒症状，血压下降，最后出现黄疸、谵妄和昏迷。  

传染病的特征

　　（一）基本特征

　　1.有病原体　每种传染病都有其特异的病原体，包括病毒、立克茨体、细菌、真菌、螺旋体、原虫等。

　　2．有传染性　病原体从宿主排出体外，通过一定方式，到达新的易感染者体内，呈现出一定传染性，其传染强度与病原体种类、数量、毒力、易感者的免疫状态等有关。

　　3．有流行性、地方性、季节性

　　（1）流行性　按传染病流行病过程的强度和广度分为。散发：是指传染病在人群中散在发生；流行：是指某一地区或某一单位，在某一时期内，某种传染病的发病率，超过了历年同期的发病水平；大流行：指某种传染病在一个短时期内迅速传播、蔓延，超过了一般的流行强度；暴发：指某一局部地区或单位，在短期内突然出现众多的同一种疾病的病人。

　　（2）地方性　是指某些传染病或寄生虫病，其中间宿主，受地理条件，气温条件变化的影响，常局限于一定的地理范围内发生。如虫媒传染病，自然疫源性疾病。

　　（3）季节性　指传染病的发病率，在年度内有季节性升高。此与温度、湿度的改变有关。

　　4．有免疫性　传染病痊愈后，人体对同一种传染病病原体产生不感受性，称为免疫。不同的传染病、病后免状态有所不同，有的传染病患病一次后可终身免疫，有的还可感染。

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。

危险因素
  获得性危险因素
  某些危险因素可增加急性深静脉血栓形成和肺栓塞的概率。全髋关节和膝关节置换术、髋部骨折于术和癌症手术，与外伤和脊髓损伤—样，都具有很高的危险性。总之，急性疾病可能是发牛血栓栓塞的最常见开端。活动明显减少也可增加患者的危险，尽管日前还不清楚能导致危险增加的活动减少的程度和持续时间，但常取决于并存的危险因素。长时间乘飞机旅行或乘坐地面交通工具旅行，可增加血栓栓塞危险。静息的生活方式和需要久坐的职业值得注意。事实上，已有人用eThrombosis 一词来描述与长时间坐在电脑终端前相关的血栓形成事件，高龄是另一个明确的危险因素，因为40岁后危险逐渐增加。
    在有癌症和血栓形成倾向的患者中，获得件危险因素和遗传易感性可能重叠。癌症时，特殊肿瘤或其治疗的促凝作用有可能增加血栓栓塞事件的危险，因为肿瘤可导致静脉阻塞，患者活动减少，需要放置中心导管以及进行化疗。抗磷脂抗体与血栓形成和反复发生不明原因流产有关。静脉血栓栓塞的遗传性和获得性危险因素列于表1。
  遗传疾病和血栓栓塞危险
  蛋白C、蛋白S和抗凝血酶缺陷，可显著增加血栓形成和血栓栓塞事件的危险。V因子Leiden(突变)可激活蛋白C抵抗，是血栓形成倾向最常见的遗传性危险因素。对下列患者最需要考虑进行有关这些障碍的检测：反复血栓栓塞的患者，年轻患者，没有明显刺激时出现血栓形成或血栓栓塞事件的患者，不常见部位(如脑、肠系膜、门静脉或肝静脉)发生血栓形成的患者。总之，Virchow经典危险三联征—淤滞、静脉损伤和高凝状态—仍然可用来评估患者，它反映了遗传和环境危险因素的影响及其相互作用。了解患者的危险因素有助于医师选择适当的诊断和预防策略。

诊断方法
  临床表现
  能够识别静脉血栓栓塞的症状和体征，可缩短诊断延迟的时间。腿痛、发热或肿胀有可能提示患者有深静脉血栓形成。  
 急性肺栓塞患者常出现呼吸困难或胸痛，可以突然发病，也可以在数天至数周内逐渐出现上述症状。胸膜炎性胸痛和咯血更多见于肺梗死患者，其特点是栓子较小，外周栓子更多，这类患者的胸膜摩擦音可能很明显。患者的咳嗽、心悸和头晕症状以及发热、喘呜和哕音等体征，有可能为肺栓塞或并存病所致。呼吸急促和心动过速很常见，但没有特异性。肺栓塞引起的肺动脉高压体征包括颈静脉充盈、P2亢进、右侧可听到S4和右心室抬举。深静脉血栓形成和肺栓塞的症状和体征可能具有高度提示性作用，但既不敏感也不特异。因此，当怀疑有深静脉血栓形成或肺栓塞的时候，必须考虑进一步检查。常常(但不总是)有这种情况，即症状的严重程度决定于血栓栓塞负荷。然而，即使外周非常大的栓子，出有可能静静地增大，然后出现症状或甚至发生致命性肺栓塞，而较小的栓子则有可能引起严重症状，尤其当心血管的功能储备已经很差时。如果患者突发晕厥或几乎晕厥、低血压、极度低氧血症、电机械分离或心脏停搏，应考虑到大面积肺栓塞的可能性。
  初步实验室检查和预测概率
  如果怀疑肺栓塞，应根据病史、体格检查和已知危险因素进行仔细评估。还应考虑其他检查项目，包括心电图、X线胸片和动脉血气分析。心电图异常，包括不明原因的心动过速，在急性肺栓塞时很常见，但不特异。急性肺源性心脏病的心电图表现，如S1、Q3、T3图形，右束支阻滞，肺性P波或电轴右偏，在发生大面积栓塞时比栓子较小时多见，但这些改变也是非特异的。X线胸片一般不能确诊，但是可以发现其他诊断。急性肺栓塞患者通常有低氧血症，但动脉血氧张力有可能正常。在罕见病例中，肺泡—动脉氧差也是正常的。患者突然发生或出现不能解释的动脉氧或氧饱和度改变时，应当疑似此病。
    其他检查也可能有用。尽管D-二聚体检查(检测交联纤维蛋白特异衍生物的血浆水平)阳性，提示可能有静脉血栓形成和肺栓塞，但这一检查是非特异的，因为感染、癌症、创伤和其他炎症状态的患者也有可能阳性，所以，不能据此决定治疗。以酶联免疫吸附测定(ELISA)为基础的D-二聚体检测法的敏感性高(96%-98%)。D-2聚体检测最好与临床概率一起考虑，后者可使用两种临床预测评分系统之—进行估计，这些评分系统可评估患者发生急性肺栓塞的可能性(表2)。有关临床概率评估的循证文献多数采用这些方法，它们基于病史和体格检查提供的信息。这些评分方法在急诊室就诊的患者中得到了最好的应用。对于预测概率低或中等水平的患者，当基于ELISA的D-二聚体检测阴性时，其发生深静脉血栓形成和肺栓塞的可能性低，无需进行特殊影像学检查。然而，对于预测概率高的患者，应进行影像学检查，而不是进行D-二聚体检测。用于进行临床概率评估的方法可能不如下述原则更重要，即必须根据每个人实际发生肺栓塞的临床概率，对每例患者进行仔细的评估。

    其他生化标志物可提供有用的临床信息。心肌肌钙蛋白水平可能升高，尤其是发生大面积急性肺栓塞的患者。肌钙蛋白水平升高最常用于已确诊肺栓塞患者的危险分层，但单独使用时不是一个敏感的诊断工具。脑钠尿肽的血浆水平随着心室张力的增加而增加，但患有充血性心力衰竭或各种可引起肺动脉高压的疾病的患者，都可能有脑钠尿肽水平升高。
  影像学检查
  很多类型的影像学检查已经用于急性肺栓塞的诊断，包括通气—灌注扫描、造影增强的计算机体层摄影(CT动脉造影、磁共振成像(MRl)、标准肺动脉造影，以及用町检出深静脉血栓形成的影像学检查(超声检查、CT静脉造影、 MRI和标准静脉造影)方法，来检查急性肺栓塞。
    造影增强的CT动脉造影优于通气—灌注扫描，包括速度、非血管性结构的特点和静脉血栓形成的检出率。如果患者有急性或慢性肾功能不全，应当慎用造影剂，因为造影剂有可能引起造影剂相关性肾病。CT动脉造影对检出肺动脉主干、肺叶动脉或肺段动脉栓子的敏感性和特异性最强。使用多排CT动脉造影可减少扫描厚度，缩短扫描时间，明显提高段和亚段血管的可视性。
   
要点提示
    约79%的肺栓塞患者有腿部深静脉血栓形成的证据。如果这些患者没有被检出深静脉血栓形成，很可能整个栓子已经脱落并已造成栓塞。
    腿痛、发热或肿胀有可能提示患者有深静脉血栓形成。急性肺栓塞患者常出现呼吸困难或胸痛，可以突然发病，也可以在数天至数周内逐渐出现。
  如果患者突发晕厥或几乎晕厥、低血压、极度低氧血症、电机械分离或心脏停搏，应考虑到大面积肺栓塞的可能性。
    肺栓塞引起的肺动脉高压体征包括颈静脉充盈、P2亢进、右侧可听到S4和右心室抬举。
    已有人用eThrombosis一词来描述与长时间坐在电脑终端前相关的血栓形成事件。
 影像学检查
  系统回顾和最近的前瞻性随机临床试验提示，对于门诊疑似肺栓塞的患者，如果CT动脉造影检查阴性，则不治疗的预后也非常好，尽管加做包括下肢超声检查在内的其他影像学检查，通常是评估的组成部分，对治疗决策有帮助。
    最近一项大规模前瞻性临床研究，人选疑似急性肺栓塞的门诊患者，研究者报告，多排CT动脉造影(该研究中唯一的影像学检查)阴性时，不启动抗凝治疗的转归非常好。但是，对于临床高度疑似肺栓塞的病例，即使CT动脉造影阴性，也应慎重考虑加做其他影像学检查。当单排或多排CT动脉造影提示急性肺栓塞时，几乎都需要治疗。 CT动脉造影假阳性的病例似乎很少见。图2显示1例急性肺栓塞患者的 CT动脉造影结果。

    某些临床研究联合使用CT动脉造影和CT静脉造影。最近，肺栓塞诊断的前瞻性研究II，比较了单独使用多排CT动脉造影和联合使用CT静脉造影检查疑似急性肺栓塞”的效果。单独使用螺旋CT动脉造影的敏感性是83%，而联合使用CT动脉造影和CT静脉造影可使敏感性提高到90%，提示联合检查有助于急性肺栓塞的处理，尤其是对复杂门诊病例的治疗。
    对于无心肺疾病的患者，通气—灌注扫描最可能做出诊断。肺灌注扫描正常可有效排除急性肺栓塞。提示急性肺栓塞概率高的扫描结果，应被视为有诊断价值，除非临床怀疑肺栓塞的可能性低，或患者既往有肺栓塞的病史且扫描结果相同。然而，如果临床病史强烈提示肺栓塞，即使通气—灌注扫描结果不能诊断，也应继续进行严格的诊断评估。对于急性肺栓塞临床概率低的患者，或临床概率为中度但D-二聚体检测结果阴性的患者，如果通气—灌注扫描不能诊断，则无需进行其他检查或治疗。最近一项临床研究连续入选221例疑似急性肺栓塞的患者，成功地使用了多技术经胸MRI，然后进行磁共振静脉造影，以寻找深静脉血栓形成和肺栓塞的证据。
    超声心动图的改变有可能强烈支持存在有血流动力学意义的肺栓塞，有可能用于指导治疗。使用这种技术偶尔可证实存在通过心脏移至肺部的栓子。另外，有人用床旁血管内超声检查观察大栓子。图3显示对疑似肺栓塞病例的诊断流程。

治疗
  抗凝治疗
  除非患者有明显(下肢)疼痛和肿胀，否则不推荐深静脉血栓形成患者卧床休息。然而，有关肺栓塞的研究资料不足以支持这条建议。因此，如果确诊肺栓塞，经常建议患者住院治疗，开始时卧床24~48小时。同样，尽管在门诊使用低分子量肝素治疗深静脉血栓形成，已得到广泛认可，该疗法可提高患者的生活质量和降低医疗费用，但有关门诊治疗急性肺栓塞的资料不太充分。
    发生急性肺栓塞时，只要没有禁忌证，都应启动肠外抗凝治疗，使用低分子量肝素、戍聚糖(fondaparinux)或普通未分组分肝素。尽管这些药物不是溶栓药，但它们可减少纤溶系统执行功能中的阻力，最终降低血栓栓塞负荷。显然，抗凝治疗可提高有症状的肺栓塞患者的生存率， 
要点提示
    对于临床高度疑似肺栓塞的病例，即使CT动脉造影阴性，也应慎重考虑加做其他影像学检查。当单排或多排CT动脉造影提示急性肺栓塞时，几乎都需要治疗。
    发生急性肺栓塞时，只要没有禁忌证，都应启动肠外抗凝治疗，使用低分子量肝素、戊聚糖 (fondaparinux)或普通未分组分肝素。
    如果疑似肺栓塞的可能性非常高，只要出血的危险似乎不会过大，甚至应在影像学检查前就考虑肠外抗凝治疗的问题。可在治疗的第一天开始使用华法林。皮下低分子量肝素或根据体重调整的静脉未分组分肝素，应至少使用5天，最好用至连续2天国际标准化比率在治疗范围 (2.0-3.0)内。
 但诊断后1年中的复发性、非致命性静脉血栓栓塞的发生危险估计为5%-10%。如果疑似肺栓塞的可能性非常高，只要出血的危险似乎不会过大，甚至应在影像学检查前就考虑肠外抗凝治疗的问题40。可在治疗的第一天开始使用华法林。皮下低分子量肝素或根据体重调整的静脉未分组分肝素，应至少使用5天，最好用至连续2天国际标准化比率在治疗范围(2.0-3.0)内。使用未分组分肝素时，应每6小时测1次活化的部分促凝血酶原激酶时间，直至其稳定在治疗范围 (对照的1.5-2.5倍)。活化的部分促凝血酶原激酶时间在24小时内达到治疗范围，似乎可降低复发的危险。尽管不能为CT动脉造影证实的孤立的亚段肺栓子制定循证治疗建议，但这些患者通常得到了治疗，因为很难明确排除腿部存留血凝块的可能性，而且这些血凝块很可能继续生成。
    全球已经研究和批准使用的低分子量肝素制剂很多。低分子量肝素和戊聚糖制剂优于未分组分肝素，包括生物利用度较高，较易预测剂量，皮下给药 (通常不需要监测)，发生肝素诱导的血小板减少症的危险较低。通过测定抗活化X因子(抗Xa因子)的活性水平，来监测低分子量肝素，可能适用于病态肥胖者(体重>150kg)或非常瘦的患者(< 40kg)，妊娠患者，有非常严重的肾功能不全或肾功能快速变化的患者。严重肾功能不全(肌酐清除率低于30ml/min)的患者不应使用戊聚糖，因为它通过肾脏排泄，肾功能不全时半衰期延长。
    随机临床研究支持用低分子量肝素或戊聚糖治疗有症状的肺栓塞、伴或不伴肺栓塞的深静脉血栓形成。治疗深静脉血栓形成时，低分子量肝素可能优于未分组分肝素，至少在降低死亡危险和降低肺栓塞初始治疗期间的大出血危险方面，与未分组分肝素等效。在急性非大面积肺栓塞的患者中，美国胸科医师学会根据1A级证据 (来自没有重大缺陷的随机临床试验的资料)，推荐使用低分子量肝素而不是普通肝素。
    低分子量肝素制剂和戊聚糖优于普通肝素之处包括良好的生物利用度，皮下给药而不是静脉使用，肝素诱发的血小板减少症发生率低。在美国，低分子量肝素的一个潜在缺点是医院药房的采买费用，然而，分析资料提示，即使在住院部，使用低分子量肝素的花费也不比未分组分肝素高。虽然低分子量肝素制剂有共同的特点，但这类药物中的不同化合物各有特点，因此，一个药物的临床试验结果和特殊适应证，有可能不适用于其他药物。
    急性静脉血栓栓塞患者需要长期抗凝治疗，以预防症状进展和血栓形成复发。对于有暂时危险因素的患者，如果发生有证据的血栓栓塞，应治疗3~6个月，但如果有意义的危险因素持续存在，或血栓栓塞是特发性的，或有既往发生静脉血栓栓塞的记录，则应延长治疗时间。最新资料提示，D-二聚体水平可能有助于指导疗程，D-二聚体水平持续升高似乎与复发率增加相关。与使用华法林相比，给癌症患者长期使用低分子量肝素(达肝素)进行针对血栓形成的治疗，与血栓栓塞复发次数较少有关。
    应考虑用直接凝血酶抑制剂(如阿加曲班或来匹卢定)治疗肝素诱导的血小板减少症伴血栓形成。直至疾病进程得到控制，血小板计数恢复正常范围后，才能启动华法林治疗，因为血栓形成性并发症有可能逐渐加重，包括静脉性肢体坏疽和华法林诱发的皮肤坏死。来匹卢定经肾脏排泄，阿加曲班经肝脏代谢——当存在肾脏或肝脏疾病时，考虑这些问题很重要。口服的直接凝血酶抑制剂如达比加群(dabigatran)和口服的抗Xa因子抑制剂如rivaroxaban和 apixaban，正在3期临床研究中，生物素化idraparinux(一种可逆的肠道外抗Xa因子抑制剂，每周仅需用药1次)也在 3期临床研究中。来自核苷酸模板的 Aptamers具有可逆性凝血因子拮抗剂的作用，有可能与一种特异性解毒药一起研发，似乎是有希望的抗凝药，但都没有获准上市。
  放置下腔静脉滤器
  放置下腔静脉滤器的主要适应证包括有抗凝治疗的禁忌证，在抗凝治疗过程中发生大出血并发症，以及患者在接受充分治疗的过程中复发栓塞。有时，如果认为还存在威胁病人生命的其他栓子，可以放置滤器以防发生大面积肺栓塞，尤其是存在溶栓治疗禁忌证时。然而，后一种适应证并不是基于强有力的临床试验资料。尽管滤器可有效降低肺栓塞的发生率，但它们增加了随后深静脉血栓形成的发生率，并且没有资料显示它们可提高患者的总生存率。理想的(可收回)滤器可长期留在原位，或当患者不再需要进行下腔静脉遮挡时可收回。某些类型的摅器可在放置数月后被收回，也有置入近一年后被取出的报道，尽管公开发表的文章中有关极晚期取出的资料很少。最近发表了有关使用下腔静脉滤器的建议。
  大面积肺栓塞的治疗
  导致血流动力学不稳定的肺栓塞称为大面积肺栓塞。一旦怀疑发生大面积肺栓塞，必须制定诊断计划和采取积极的措施。大面积肺栓塞时的病理生理学改变可导致右心室功能衰竭，从而影响左心室前负荷，后者有可能是致命性的。如果患者发生低血压需要输注盐水，治疗时应非常小心。如果血压没有很快恢复，应考虑进行血管加压药 (如多巴胺)治疗，总的来说，几乎没有关于使用正性肌力药的资料。必要时，可采用吸氧、气管插管和机械通气治疗呼吸衰竭。
  溶栓治疗的并发症
  得到最广泛接受的溶栓治疗适应证，是证实存在肺栓塞合并心源性休克。当患者出现全身低血压但没有休克时，也常常考虑进行溶栓治疗。在发生次大面积栓塞——即肺栓塞引起右心室扩大和活动减弱，但没有全身低血压时，使用溶栓治疗是有争议的。没有规模足够大的临床试验能够提供明确的数据，证明该疗法对这类病例有生存益处。与单独使用肝素相比，t-PA与肝素同时使用时，需要增加治疗的可能性较小。链激酶、尿激酶和重组的组织纤溶酶原激活剂(t-PA)已经得到广泛研究，可以较快速输注的t-PA是应用最广泛的溶栓药。
    血浆肌钙蛋白水平升高，可识别有可能从更积极的治疗中获益的血压正常的亚组患者。也可考虑给下列患者进行溶栓治疗：氧合情况严重受损的患者，或影像学检查发现有巨大栓塞负荷的病人——即使不存在血流动力学不稳定的问题，或广泛静脉血栓形成伴非大面积 (肺)栓塞的患者。然而，支持这些适应证的循证资料有限，需要个体化治疗。
    溶栓治疗最严重的并发症是颅内出血，尽管临床试验中报告的发生率<1%，一项大规模注册研究中的发生率约为3%TM。其他并发症包括腹膜后和胃肠道出血，手术伤口出血或最近进行介入治疗的部位出血。应考虑的禁忌证包括颅内、脊髓或眼睛手术或疾病，近期接受大手术或其他有创操作，活动件大出血或近期发生大出血，妊娠以及临床明显的出血危险。颅内出血是最明确和最强的禁忌证。进行临床判断时必须权衡利弊。可考虑施行基于导管的机械性肺动脉栓子摘除术和 (或)局部栓子内溶栓治疗。肺动脉栓子摘除术有可能成功治疗证实存在大面积肺栓塞和血流动力学不稳定的患者，或溶栓治疗失败或有溶栓禁忌证的患者。然而，这些患者的情况很不稳定，死亡的危险高。当存在右心血栓形成时，无论伴或不伴反常栓塞，有时可考虑手术治疗，但还没有随机临床试验资料支持此做法，对这类病例往往考虑溶栓治疗。
图4显示一般的治疗流程。
  预后
  多数接受充足抗凝药治疗的急性肺栓塞患者存活。据报道，3个月的总病死率约为15%-18%。患者就诊时处于休克状态，与病死率增加2-6倍相关，休克患者中的多数死亡病例在就诊后1小时内死亡。慢性腿痛和肿胀(血栓形成后综合征)和慢性血栓栓塞性肺动脉高压，可能是急性肺栓塞的长期后遗症12。
  预防
  住院患者的静脉血栓栓塞危险大，但当患者接受了适当的预防性治疗后，该危险可显著下降。研究证实，肝素、低分子量肝素、戊聚糖、华法林和机械性预防治疗，在不同的临床情况下有效。不幸的是，根据美国和国际性研究的资料，预防性措施似乎总体使用不足。抗凝药预防比卜肢机械性预防更有效，但应考虑在具体患者中的血栓形成和出血的危险“。
    最近的共识声明为各种临床情况提供了重要的指导意见。某些患者群发生静脉血栓形成和肺栓塞的危险尤其高。在全髋关节或膝关节置换术后，如果不采取预防措施，静脉血栓形成的危险>50%。外伤和脊髓损伤也是非常高危的情况。有研究证实，在这四种情况下，用低分子量肝素进行预防都优于普通的未分组分肝素。在接受全髋关节置换和髋关节骨折手术的病例中，戊聚糖是一种有效的预防药物。在其他情况卜，如接受腹部手术的病例，低剂量未分组分肝素似乎已足够，尽管应该考虑到，就患者和护理工作而言，使用低分子量肝素对多数适应证都有优势。
    一项采用静脉造影终点的大规模研究提示，在急症住院的患者中，如不采取预防措施，静脉血栓栓塞的危险有可能高达15%。在这个人群中，设计良好的前瞻性随机临床试验证实，依诺肝素(enoxaparin)L5、达肝素(daheparin)和戊聚糖在预防急性静脉血栓栓塞方面，都优于安慰剂。在内科患者中每天使用1次依诺肝素至少与每8小时使用1次(普通)肝素的效果相同，在脑卒中患者中，与每12小时使用5000单位末分组分肝素预防相比，使用依诺肝素预防与深静脉血栓形成的发生率显著较低相关。脑卒中或充血性心力衰竭患者的危险尤其高，在后一组患者中，左心室功能障碍的程度可能与血栓形成的危险相关。在限制活动的内科患者中，延长依诺肝素预防性治疗时间 (约38天)与7-10天的预防相比，前者似乎能降低深静脉血栓形成的发生率，这种延长的预防性治疗已经证明对某些高危人群有效，如接受全髋关节置换的患者，或因癌症接受手术的患者。
    与治疗静脉血栓栓塞时—样，给有显著肾功能不全的患者使用低分子量肝素进行预防时，应考虑减少剂量，否则，应使用普通肝素。对于危险非常高的内外科患者或危重症患者，联合使用抗凝疗法和机械方法是合理的。在专家共识意见中，不赞成给外伤和接受神经手术的患者使用下腔静脉滤器作为一级预防，尽管其他学者推荐给某些外伤患者预防性置入下腔静脉滤器”。
    应评估每例住院患者对预防措施的需求，所有医院都应根据现有医学文献，制定适用于每种特定临床情况的书面指南。美国已经开展了几个项目，努力优化急性静脉血栓栓塞的预防和治疗策略。由Medicare(政府出资的老年人医疗照顾方案)和Medicaid(低收入人群的医疗补助方案)服务机构、美国医学会和其他医学相关机构推出的改善外科治疗伙伴计划(Surgical Care lmprovementPartnership)，已将预防静脉血栓栓塞纳入需要改善的目标领域，国家质量论坛和医疗保健组织认证联合会(现称为联合会)，正在完成执行措施的终稿，以确保对所有住院患者都能考虑到血栓栓塞的危险和相关预防措施“。致死性肺栓塞的发生率高得令人无法接受，它应受到更多关注，以确保给这峰患者使用最传预防措施。妊娠和急性肺栓塞
    妊娠或产后妇女以及正在接受激素治疗的女性，发生静脉血栓栓塞的危险增加，这些人群值得特别关注。最近，美国流行病学资料显示，妊娠或产后妇女的静脉血栓栓塞相对危险为4.29，总发病率为199.7例／10万妇女—年。此外，第一次发生静脉血栓栓塞的危险，在产后期是妊娠期的5倍，产后期发生肺栓塞的危险是妊娠期的15倍。小剂量口服避孕药使静脉血栓形成的危险增加2-5倍，激素替代治疗似乎可使血栓栓塞的危险增加2～4倍。对于疑似急性肺栓塞的妊娠患者，似乎理想的策略是使用无创诊断法，而不进行影像学检查，但在必要时，不能因为担心暴露于射线而阻止临床医师使用CT动脉造影或通气—灌注扫描。对于发生急性静脉血栓栓塞的妊娠患者，在需要进行肠外抗凝治疗、放置厂腔静脉滤器或施行栓子切除术时，应采取与其他患者相同的初始治疗方案。对于发生致命性肺栓塞的患者，不能仅仅因为妊娠就不使用溶栓治疗。长期抗凝最好使用低分广量肝素，因为华法林是一种致畸原。

结论
    不治疗的肺栓塞与高病死率相关。疑似肺栓塞日寸需要立即进行诊断检查，评估危险因素和临床概率，必要时可进行经验性临床评估和使用得到认证的临床预测积分。临床评估联合D-二聚体检查，有时可避免进——步影像学检查。否则，应降低进行诊断性影像学检查的门槛。研究显示，对急性肺栓塞进行治疗可降病死率。有必要对该病患者进行危险分层，以便就使用溶栓治疗的问题做出最佳决策。预防工作至关重要。(N Engl J Med 2008；358：1037-52  March 6 2008)  

2007年11月号的《Academic Emergency Medicine》(AEM)罕见的以全册内容讨论了急诊医学范畴内循证医学证据、医学进展与新知向临床实践转化的问题。本册内容的背景是—— May 15, 2007, Academic Emergency Medicine sponsored a consensus conference with a goal of establishing a research agenda for the specialty of emergency medicine (EM), aimed at facilitating knowledge translation (KT)。

这是一个非常非常值得关注的现象，这意味着美国急诊医学会也将和当年美国的危重医学学会一样，有通过组织编撰“基于循证的临床诊治指南”甚至创立所谓的“***运动”的端倪，其目的无疑是要带动整个行业实践模式的转换和整体水平的提高——本册内容显然就是这个目的，不过显得更为高明一点—— 由于急诊科室的特殊性，人员和设备的短缺导致相关专业进展难以在急诊室得到有效普及，或者被斥之为加剧资源调配紧张，也使从业人员对新指南或新的临床证据依从性不足。现在看来，急诊医务工作者将医学新知转化为临床实践的重要性远比单纯循证进展的继续教育重要得多。本册内容就是对症下药，强调了前者的重要性，并请来多位在急诊室开展过相关研究的作者现身说法，比如我们之前提到的Nguyen，另外一位就是Jones，这两个作者都是将早期目标治疗（EGDT）用于急诊室的先驱，他们的想法与动机实在是值得我们认真学习！

从另外一个角度来看，“急诊监护化”的趋势越来越明显，重症监护医学与急诊医学的交叉性恐怕会越来越大。以早期目标治疗(EGDT)为例，当初Rivers创立该方案是在监护内，但是现在的趋势是在急诊室推广EGDT显然更能突出“早期”的内涵，对提高患者生存率的价值更有意义（患者进入ICU后才开始EGDT恐怕为时过晚）。因此本册《Academic Emergency Medicine》可以说是急诊医学开始全方位提高整体医疗实践水平呼声的一种反映和尝试，我们拭目以待国内国际下一步的相关动态。

COMMENTARIES:

Executive Summary: Knowledge Translation in Emergency Medicine: Establishing a Research Agenda and Guide Map for Evidence Uptake

Eddy S. Lang, Peter C. Wyer, and Barnet Eskin
Acad Emerg Med 2007 14: 915-918; published online before print October 8 2007, 10.1197/j.aem.2007.07.005 [Full Text] [PDF]  

 

The Development of the Academic Emergency Medicine Consensus Conference Project on Knowledge Translation

Eddy S. Lang, Peter C. Wyer, Barnet Eskin, Christos Tselios, Marc Afilalo, and James G. Adams
Acad Emerg Med 2007 14: 919-923. [Full Text] [PDF]  

 

The Knowledge Translation Paradigm: Historical, Philosophical, and Practice Perspectives

Jerris R. Hedges
Acad Emerg Med 2007 14: 924-927; published online before print August 17 2007, 10.1197/j.aem.2007.06.016 [Full Text] [PDF]  

 

Responsiveness to Change: A Quality Indicator for Assessment of Knowledge Translation Systems

Peter C. Wyer
Acad Emerg Med 2007 14: 928-931; published online before print August 13 2007, 10.1197/j.aem.2007.06.013 [Full Text] [PDF]  

 

CONFERENCE PRESENTATIONS:

Keynote Address: Closing the Research-to-practice Gap in Emergency Medicine

Carolyn M. Clancy
Acad Emerg Med 2007 14: 932-935; published online before print October 4 2007, 10.1197/j.aem.2007.06.028 [Abstract] [Full Text] [PDF]  

 

Some Theoretical Underpinnings of Knowledge Translation

Ian D. Graham, Jacqueline Tetroe KT Theories Research Group
Acad Emerg Med 2007 14: 936-941. [Abstract] [Full Text] [PDF]  

 

Decision Support Technology in Knowledge Translation

Brian R. Holroyd, Michael J. Bullard, Timothy A.D. Graham, and Brian H. Rowe
Acad Emerg Med 2007 14: 942-948; published online before print August 31 2007, 10.1197/j.aem.2007.06.023 [Abstract] [Full Text] [PDF]  

 

Guideline Implementation Research: Exploring the Gap between Evidence and Practice in the CRUSADE Quality Improvement Initiative

Andra L. Blomkalns, Matthew T. Roe, Eric D. Peterson, E. Magnus Ohman, Elizabeth S. Fraulo, and W. Brian Gibler
Acad Emerg Med 2007 14: 949-954. [Abstract] [Full Text] [PDF] [Appendix A] [Figure 7]   

 

Implementation of Clinical Decision Rules in the Emergency Department

Ian G. Stiell and Carol Bennett
Acad Emerg Med 2007 14: 955-959; published online before print October 8 2007, 10.1197/j.aem.2007.06.039 [Abstract] [Full Text] [PDF]  

 

Evidence-based Reviews and Databases: Are They Worth the Effort? Developing Evidence Summaries for Emergency Medicine

Peter C. Wyer and Brian H. Rowe
Acad Emerg Med 2007 14: 960-964; published online before print August 29 2007, 10.1197/j.aem.2007.06.011 [Abstract] [Full Text] [PDF]  

 

Funding Opportunities in Knowledge Translation: Review of the AHRQ's "Translating Research into Practice" Initiatives, Competing Funding Agencies, and Strategies for Success

Michael Handrigan and Jean Slutsky
Acad Emerg Med 2007 14: 965-967. [Abstract] [Full Text] [PDF]  

 

Bridging the Gap between Clinical Research and Knowledge Translation in Pediatric Emergency Medicine

Lisa Hartling, Shannon Scott-Findlay, David Johnson, Martin Osmond, Amy Plint, Jeremy Grimshaw, Terry P. Klassen Canadian Institutes for Health Research Team in Pediatric Emergency Medicine
Acad Emerg Med 2007 14: 968-977. [Abstract] [Full Text] [PDF]  

 

CONSENSUS WORKSHOP SESSIONS:

Development of the Capacity Necessary to Perform and Promote Knowledge Translation Research in Emergency Medicine

Peter S. Dayan, Martin Osmond, Nathan Kuppermann, Eddy Lang, Terry Klassen, David Johnson, Sharon Strauss, Erik Hess, Sandra Schneider, Marc Afilalo, and Martin Pusic
Acad Emerg Med 2007 14: 978-983. [Abstract] [Full Text] [PDF]  

 

Cognitive and Social Issues in Emergency Medicine Knowledge Translation: A Research Agenda

Jamie C. Brehaut, Robert Hamm, Sumit Majumdar, Frank Papa, Alison Lott, and Eddy Lang
Acad Emerg Med 2007 14: 984-990; published online before print September 24 2007, 10.1197/j.aem.2007.06.025 [Abstract] [Full Text] [PDF] [Appendix A: Search Strategy]   

 

Knowledge Translation Consensus Conference: Research Methods

Scott Compton, Eddy Lang, Thomas M. Richardson, Erik Hess, Jeffrey Green, William Meurer, Rachel Stanley, Robert Dunne, Shannon Scott-Findlay, Rahul K. Khare, and Jeremy Grimshaw
Acad Emerg Med 2007 14: 991-995. [Abstract] [Full Text] [PDF]  

 

Informatics and Knowledge Translation

Michael J. Bullard, Stephen D. Emond, Tim A.D. Graham, Kendall Ho, and Brian R. Holroyd
Acad Emerg Med 2007 14: 996-1002. [Abstract] [Full Text] [PDF]  

 

The Emergency Physician and Knowledge Transfer: Continuing Medical Education, Continuing Professional Development, and Self-improvement

Barbara J. Kilian, Louis S. Binder, and Julian Marsden
Acad Emerg Med 2007 14: 1003-1007. [Abstract] [Full Text] [PDF]  

 

Graduate Medical Education and Knowledge Translation: Role Models, Information Pipelines, and Practice Change Thresholds

Barry M. Diner, Christopher R. Carpenter, Tara O'Connell, Peter Pang, Michael D. Brown, Rawle A. Seupaul, James J. Celentano, Dan Mayer KT-CC Theme IIIa Members
Acad Emerg Med 2007 14: 1008-1014. [Abstract] [Full Text] [PDF]  

 

Toward Improved Implementation of Evidence-based Clinical Algorithms: Clinical Practice Guidelines, Clinical Decision Rules, and Clinical Pathways

Gary M. Gaddis, Peter Greenwald, and Sue Huckson
Acad Emerg Med 2007 14: 1015-1022. [Abstract] [Full Text] [PDF]  

 

Effective Synthesized/preappraised Evidence Formats in Emergency Medicine and the Use of Supplemental Knowledge Translation Techniques

Brian H. Rowe, Barry Diner, Carlos A. Camargo, Jr., Andrew Worster, Antoinette Colacone, Peter C. Wyer Knowledge Translation-Consensus Conference Theme Ib Members
Acad Emerg Med 2007 14: 1023-1029. [Abstract] [Full Text] [PDF]  

 

The Use of Health Care Policy to Facilitate Evidence-based Knowledge Translation in Emergency Medicine

Charlene B. Irvin, Marc Afilalo, Scott C. Sherman, Steven J. Stack, Sue Huckson, Amy Kaji, and Barnet Eskin
Acad Emerg Med 2007 14: 1030-1035; published online before print August 31 2007, 10.1197/j.aem.2007.06.022 [Abstract] [Full Text] [PDF]  

 

Public Health Considerations in Knowledge Translation in the Emergency Department

Steven L. Bernstein, Edward Bernstein, Edwin D. Boudreaux, Charlene Babcock-Irvin, Michael J. Mello, Atul K. Kapur, Bruce M. Becker, Richard Sattin, Victor Cohen, and Gail D'Onofrio
Acad Emerg Med 2007 14: 1036-1041; published online before print August 15 2007, 10.1197/j.aem.2007.06.012 [Abstract] [Full Text] [PDF]  

 

Knowledge Translation at the Macro Level: Legal and Ethical Considerations

Gregory Luke Larkin, Cara J. Hamann, Edward P. Monico, Linda Degutis, Jeremiah Schuur, Walter Kantor, and Charles S. Graffeo
Acad Emerg Med 2007 14: 1042-1046. [Abstract] [Full Text] [PDF]  

 

Knowledge Translation in International Emergency Medical Care

L. Kristian Arnold, Hisham Alomran, V. Anantharaman, Pinchas Halpern, Mark Hauswald, Pia Malmquist, Elizabeth Molyneux, Bishan Rajapakse, Megan Ranney, and Junaid Razzak
Acad Emerg Med 2007 14: 1047-1051. [Abstract] [Full Text] [PDF]  

 

Knowledge Translation in the Emergency Medical Services: A Research Agenda for Advancing Prehospital Care

David C. Cone
Acad Emerg Med 2007 14: 1052-1057; published online before print August 29 2007, 10.1197/j.aem.2007.06.014 [Abstract] [Full Text] [PDF]  

 

ORIGINAL CONTRIBUTIONS:

Closing Evidence to Practice Gaps in Emergency Care: The Australian Experience

Susan Huckson and Jan Davies
Acad Emerg Med 2007 14: 1058-1063; published online before print August 17 2007, 10.1197/j.aem.2007.06.015 [Abstract] [Full Text] [PDF]  

 

Qualitative Data Collection and Analysis Methods: The INSTINCT Trial

William J. Meurer, Shirley M. Frederiksen, Jennifer J. Majersik, Lingling Zhang, Annette Sandretto, and Phillip A. Scott
Acad Emerg Med 2007 14: 1064-1071; published online before print July 24 2007, 10.1197/j.aem.2007.05.005 [Abstract] [Full Text] [PDF] [Data Supplement]   

 

Implementing Early Goal-directed Therapy in the Emergency Setting: The Challenges and Experiences of Translating Research Innovations into Clinical Reality in Academic and Community Settings

Alan E. Jones, Nathan I. Shapiro, and Michael Roshon
Acad Emerg Med 2007 14: 1072-1078; published online before print July 13 2007, 10.1197/j.aem.2007.04.014 [Abstract] [Full Text] [PDF]  

 

The Utility of a Quality Improvement Bundle in Bridging the Gap between Research and Standard Care in the Management of Severe Sepsis and Septic Shock in the Emergency Department

H. Bryant Nguyen, Elizabeth Lea Lynch, Joshua A. Mou, Kristopher Lyon, William A. Wittlake, and Stephen W. Corbett
Acad Emerg Med 2007 14: 1079-1086; published online before print October 8 2007, 10.1197/j.aem.2007.06.024 [Abstract] [Full Text] [PDF]  

 

Diffusion of Medical Progress: Early Spinal Immobilization in the Emergency Department

Mark Hauswald and Darren Braude
Acad Emerg Med 2007 14: 1087-1089; published online before print July 12 2007, 10.1197/j.aem.2007.04.020 [Abstract] [Full Text] [PDF]  

 

Knowledge Translation of the American College of Emergency Physicians Clinical Policy on Hypertension

Jill F. Lehrmann, Paula Tanabe, Brigitte M. Baumann, Molly K. Jones, Zoran Martinovich, and James G. Adams
Acad Emerg Med 2007 14: 1090-1096; published online before print September 26 2007, 10.1197/j.aem.2007.05.016 [Abstract] [Full Text] [PDF]  

 

Impact of Human Factor Design on the Use of order Sets in the Treatment of Congestive Heart Failure

Stewart Reingold and Erik Kulstad
Acad Emerg Med 2007 14: 1097-1105; published online before print August 10 2007, 10.1197/j.aem.2007.05.006 [Abstract] [Full Text] [PDF] [Emergency Department CHF Standing orders]   

 

Barriers to Metered-dose Inhaler/spacer Use in Canadian Pediatric Emergency Departments: A National Survey

Martin H. Osmond, Madlen Gazarian, Richard L. Henry, Tammy J. Clifford, Jennifer Tetzlaff PERC Spacer Study Group
Acad Emerg Med 2007 14: 1106-1113; published online before print August 15 2007, 10.1197/j.aem.2007.05.009 [Abstract] [Full Text] [PDF]  

 

Implementation of an Emergency Department–based Transient Ischemic Attack Clinical Pathway: A Pilot Study in Knowledge Translation

Michael D. Brown, Mathew J. Reeves, Ted Glynn, Arshad Majid, and Rashmi U. Kothari
Acad Emerg Med 2007 14: 1114-1119; published online before print June 28 2007, 10.1197/j.aem.2007.04.019 [Abstract] [Full Text] [PDF] [TIA Clinical Pathway]   

 

CONSENSUS CONFERENCE PARTICIPANTS:

2007 Consensus Conference Participants

Acad Emerg Med 2007 14: 1120-1123. [Full Text] [PDF]  

食物名称	蛋白质含量/克
瘦猪肉   瘦牛肉   瘦羊肉   猪肝   鸡肉   虾皮   大黄鱼   带鱼   鲤鱼   鸡蛋   鸭蛋   牛奶	16.7   20.3   17.3   21.3   21.5   39.3   17.6   18.1   20.0   14.7   8.7   3.3

食物名称	蛋白质含量/克
大米   面粉   玉米面   黄豆   花生仁   鲜蘑菇   菠菜   油菜   红薯   大白菜   黄瓜   胡萝卜	7.1   10.0   3.6   36.3   26.2   2.9   2.4   1.9   1.8   1.1   0.8   0.6

2008版拯救脓毒症国际指南更新版发布

   大家注意：这是转自黄教授的个人博客的原创内容。

 今天读到《Intensive care medicine》的提前发布栏目，竟然看到“Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008”—— 老天，拯救脓毒症的严重感染性休克治疗指南2008版 已经在12月4号发布了！亏了我成天号称书海遨游，竟然不知这么大的事情发生，惭愧！全文下载链接：http://www.91files.com/?H9CL8L8JRB7PCQ0OEQS3

     和2004年的SSC指南发布时的11个国际组织46位专家比较，本次指南的撰写队伍少有变化，署名作者23名，但指南委员会有55位专家，15个学术组织参加（增加了日本的急性病学会、日本监护医学会，德国脓毒症协会以及拉丁美洲脓毒症协会等），但是非常奇怪的是参加了2004年第一版指南发布的美国胸科协会（ATS）和我们之前说过的危重病学重镇澳大利亚暨新西兰危重病协会在这次修订中并没有参加，原因不详这也是很值得玩味的事情。2004年曾经闹出拒绝参加，公开炮轰指南有铜臭气的美国感染性疾病协会这次仍然没有参与。同时由于2006年底活性蛋白C事件的公开，本次指南的开篇用罕见的极大的篇幅谈及此次修订过程的纯洁和清廉，最后还公布了所有委员的“经济利益冲突”的名单。（关注一下指南主席Dr. Dellinger，美国名宿Dr. Angus和欧洲巨擎Dr. Vincent的赞助就知道什么叫国际影响了，尤其是后者，简直太过分了！明年我到布鲁塞尔一定要当面问问他，他哪来的这么大的人格魅力:-)）。这次指南编订过程按照官方的说法没有赞助商地参加与干预，因此也没有出现赞助商的名号（我相信明眼人都知道赞助商隐藏在什么地方了...）。

         值得一提的是在参考文献部分引文共计341篇（2004年是135篇），看来进展还是太多了，难怪老黄我总是没有休息喘息的感觉；这次编辑细心的把各个章节对应的文献分列开，非常便于查询。

关于指南按照循证分级进行的程序就不多说了，具体的结论如下（括号里黑体是2008推荐等级，蓝字为2004年推荐等级），：

RESULTS: 

early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C，B); blood cultures prior to antibiotic therapy (1C, D); imaging studies performed promptly to confirm potential source of infection (1C,E); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B,D) and severe sepsis without septic shock (1D,E); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C,E); administration of either crystalloid or colloid fluid resuscitation (1B,C); fluid challenge to restore mean circulating filling pressure (1C,E); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure >/=65 mmHg (1C,D); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C,E); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C,C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patient,B). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B,B); a low tidal volume (1B,B) and limitation of inspiratory plateau pressure strategy (1C,B) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C,E); head of bed elevation in mechanically ventilated patients unless contraindicated (1B,C); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A,E); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B,B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B,B); avoidance of neuromuscular blockers, if at all possible (1B,E); institution of glycemic control (1B,D) targeting a blood glucose <150[mg/dL after initial stabilization ( 2C,D ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B,B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A,A) or proton pump inhibitors (1B,A); and consideration of limitation of support where appropriate (1D,E). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B).

看明白了吗（部分2004年的评级是靠印象，不一定记得准）？由于想第一时间报道这个大事件，所以目前全文我并没有仔细看，主要是把摘要发出来，并与原指南进行简要比较。以下是个人的初步印象，会随着阅读的进行逐渐调整。此外关于指南正文中的我们这里没有提及的一些内容，比如旧指南中没有提及的新疗法或者新方向等，我们会逐渐阐释的。

一定要强调的是，这次指南的修订中证据的分级标准（GRADE）发生了变化，和2004年的A-E级不同，这次是A-D级，因此读者在阅读的时候，要知道分级标注的变化,不要误以为证据等级真的提高了。—— 2007-12-12 注

感觉这次指南的修订几乎对既往的各种治疗方案的推荐等级都做了或多或少的“拔高”，尤其是大大提高了临床最常用治疗手段的等级，比如抗生素和血管活性药物的等级，这一方面说明相关证据的积累确实到达了应有的高度（从引文数量就能看出）；也说明在循证医学的要求下，很多经验性治疗又得到了重新的评估和证明。

部分有争议的内容，比如活性蛋白C以及激素应用的推荐等级则维持原状，这倒是比较出乎我的意料之外（尽管我们在之前的Blog中已经知道活性蛋白C的推荐等级不变，见blog1和blog2），但是仅有的一项临床3期实验PROWESS就能让APC至今金枪不倒，后续研究并没有完全证明其疗效呀，因此之后肯定会有人提出反面意见的（见blog3）。激素治疗的CORTICUS也是以失败而告终，但是这次仍然没有改变其推荐等级——不过我对激素的态度正好和APC相反，我强烈支持小剂量激素的应用。此外血糖控制这次推荐等级有所提高。

最令人意外的是早期目标指标这个“集束化”策略中的最最最核心部分却由B级倒退为C级，这倒是很有意思的现象。不过因为还没有看全文，不能说出具体原因——因为我的印象和BLOG中已经不止一次提及EGDT为核心的集束化治疗策略在急诊室和ICU逗得到初步的印证...等看全文就知道了！

其他的就等我看完全文再说吧。

最后为了能具体说明2004年各方案的等级，我把当年的官方幻灯放在下面以资对照（其中一张颜色不同的是我自己的幻灯片节选，做的还行吧，o(∩_∩)o...）：

临床问题
    美国—欧洲共识会议将急性肺损伤定义为：迅速出现气体交换障碍[动脉氧分压(mmHg)与Fi02的比值<300]，在没有充血性心力衰竭的情况下出现双侧肺泡或间质浸润。急性肺损伤的发生率为86例/10万人—年，死亡率为 39%。在美国，每年估计有19.06万例急性肺损伤病例，导致7.45万例患者死亡，治疗这些病例需要360万个住院日。ARDS是一种更严重的肺损伤，定义为动脉血氧分压与Fi02的比值低于200。ARDS的发生率是64例/10万人—年，死亡率是40％-50％。导致 ARDS的常见原因有脓毒症(有或没有肺部感染灶)、创伤、误吸、多次输血、胰腺炎、吸人性肺损伤和某些类型的药物中毒。

Figure 1. Normal Rat Lungs and Rat Lungs after Receiving High-Pressure Mechanical Ventilation at a Peak Airway Pressure of 45 cm of Water.
After 5 minutes of ventilation, focal zones of atelectasis were evident, in particular at the left lung apex. After 20 minutes of ventilation, the lungs were markedly enlarged and congested; edema fluid filled the tracheal cannula. Adapted from Dreyfuss et al.8 with the permission of the publisher. 

Table 1. Settings for Positive End-Expiratory Pressure (PEEP), According to the Required Fraction of Inspired Oxygen (FIO2). 


 病理生理学特征和疗效
  从生理学上，可将急性肺损伤定义为在肺静脉静水压不升高的情况下，由肺水肿导致的急性呼吸衰竭。该综合征的特征是弥漫性肺泡损害伴肺泡—毛细血管膜通透性增加。水肿液和血浆蛋白从血管系统渗漏到肺泡腔中。巨噬细胞和中性粒细胞在肺间质中聚集，致炎细胞因子释放到肺中。肺泡中有透明膜形成。在ARDS病人中，肺表面活性物质的化学成分和功能活性可以发生改变，导致表面张力升高，并有可能促进局部肺泡萎陷。气体交换的效率急剧恶化。
    气管插管和机械通气几乎是治疗 ARDS严重低氧血症时必不可少的手段。在过去，通气的主要目标是提高动脉水平至可接受范围(原则上，动脉血氧饱和度达88%~95%，并且二氧化碳分压和pH也应正常)。这一目标在使用高Fi02和高分钟通气量时通常都可达到。潮气量相应提高。虽然各地临床实践有些差异，但通常采用10-15 ml／ kg体重的潮气量(相比之下，静息状态下自主呼吸控制时的正常潮气量是5～ 7ml／kg)。“肺复张”(即先前萎陷的肺泡重新开放)的概念被认为是进行这种大容量通气的依据。最近，人们开始认识到，机械通气虽然有可能拯救生命，但也可以导致肺损伤加重。这种现象被称为呼吸机相关性肺损伤(图1)。肺水肿和肺不张导致 ARDS病人充气的肺体积明显减少。其结果是，使用大潮气量通气治疗有可能使相对正常的充气肺区过度膨胀。由于无充气的肺组织比正常肺组织僵硬，因此，肺顺应性下降，气道压升高。过大的容量和过高的压力，以及相应的高跨肺压(气道与胸腔之间的压力差)，造成呼吸机相关性肺损伤：另外，在未充气的异常肺泡附近，正常肺泡的充气可产生很高的剪切力，从而造成肺实质损伤，即使在施加最小的压力时也如此’。肺过度膨胀的后果包括直接生理性损害 (肺泡上皮和毛细血管内皮破坏)，以及诱发炎症反应(细胞因子和其他介质释放)。一些证据表明，在呼吸机相关性肺损伤期间诱发的炎症反应有全身性后果，与ARDS病人多系统器官衰竭的发病机制有关。
    1993年，美国胸科医师学会的一次共识会议建议，在平台压≥35 cm H20的ARDS病人中，应将使用的潮气量减少，尽管这种减少可引起一定程度的高碳酸血症(有时称为许可性高碳酸血症)。这个建议主要基于来自动物研究的资料，因为当时极少有小潮气量通气的临床研究，也没有显示这种方法对转归有益的确切资料。后来有入主张使用PEEP作为一种支持氧合的手段，但也观察到过高的PEEP可能有不良作用。有关PEEP在小潮气量通气策略中的作用和最佳应用问题尚未确定，原因是缺乏研究该问题的临床试验资料。

    临床证据
提供直接证据表明ARDS病人采用小潮气量通气有潜在益处的最早一项重要随机临床试验，发表于1998年。Amato等人在53例病人中比较了常规通气与小潮气量“保护性通气”策略(图2)。常规通气采用12ml/kg体重的潮气量、低PEEP和35-38mmHg的二氧化碳分压。保护性通气采用≤6ml／ kg的潮气量、高PEEP和许可性高碳酸血症。接受保护性通气者的28天死亡率显著低于接受常规通气者(38％对 71%)。另外，保护性通气组的临床耳气压伤病例显著减少，撤机率显著提高。虽然有些人对这项研究中常规通气组的高死亡率提出批评，但被研究的病人都是病情极重者(每例病人平均有3.6个器官衰竭)。
    在随后一项由急性呼吸窘迫综合征协作网(ARDSNet)进行的更大规模研究中，861例患有急性肺损伤或ARDS的病人被随机分配接受12ml／kg或6ml／kg预计体重的潮气量进行通气支持治疗。虽然潮气量是操纵变量，但通气策略的主要目标是将气道平台压维持在30cmH20以下，因此，接受6 mi／kg预计体重潮气量通气治疗的病人组经常被称为低牵张(low-stretch)组。低牵张策略与死亡率显著降低相关 (31％对采用12ml／kg预计体重潮气量进行通气的40％)。因此，现有的最佳证据是，采用潮气量为6ml／kg预计体重的通气策略来治疗急性肺损伤或ARDS病人。
    在相同时期进行的另外3项小规模随机临床试验，没有证实小潮气量通气对急性肺损伤或ARDS病人有益。研究结果出现这种明显不一致的原因尚不清楚，但其中可能包括每项研究中常规通气所需的气道压存在差异。—些临床研究显示，伴有气道压显著升高的常规通气具有显著生存益处。这一结果表明，小潮气量通气的益处与平台压密切相关。但是，平台压与通气导致损伤危险之间的关系可能是连续性的，因为后续资料不能证实气道压低于某一阈值后就不再有害的观念。另外，有证据表明，小潮气量或低气道压的情况下仍有可能发生肺过度膨胀，这取决于充气不良或未充气肺组织的数量”。此外，正如前述，从理论上讲，高剪切力可能造成正常与异常肺组织连接处损伤，即使施加的压力低于30cmH20时也如此。

临床使用
    小潮气量通气应被用作急性肺损伤或ARDS病人的广泛危重症治疗策略之一。初始潮气量应该使用6 ml／kg预计(而非实际)体重，如在ARDSNet研究中那样。预计体重(PBW)计算如下：
    对于男性，PBW=50.0+0.91(身高厘米数-152.4)；
    对于女性，PBW=45.5+0.91(身高厘米数-152.4)。
这种处理所使用的基本理念是，它可使潮气量与肺容积的匹配关系正常化，因为已知肺容积主要取决于身高和性别。例如，一例理想体重为70ks、后来体重增加35kg的病人，其肺容积与体重为70kg时基本相同，不能仅因为体重增加而接受较大潮气量的通气治疗。
    初始呼吸频率应设在18-22次／分范围内。这一频率稍高于其他通气方案采用的频率，这种做法旨在维持足够高的分钟通气量，以防止明显高碳酸血症。然而，在使用小潮气量通气时预期会有一定程度的高碳酸血症。理想的情况下，二氧化碳分压应逐渐升高，以防止急性酸血症，并确保血流动力学稳定。有关二氧化碳分压和pH的特定目标值尚存在争论，尽管一些临床医师主张继续执行当前指南的规定，将二氧化碳分压保持在80 mmHg以下和pH保持在7.20以上。尽管有人曾经提倡使用碳酸氢钠将pH维持在可接受水平，但这种做法在理论上存在争议，在实践中极少有这种必要。事实上，在ARD SNet研究中，低牵张组患者的平均二氧化碳分压通常都可达到低于50mmHg的水平。
    在治疗初期，应根据气道平台压来评估小潮气量通气的疗效。目标是将平台压(即吸气末停顿时的压力)维持在30 cmH20或以下，如果超过该目标，则应进一步减少潮气量至最小4 ml／kg预计体重。必须引起重视的是胸壁僵硬的病人(例如有大量腹水的病人)。在这种病人中，合理的做法是允许平台压值增加到30 cm H20以上，因为这种病人的胸腔压升高而跨肺压不升高(即并不一定有肺泡过度膨胀)。对于平台压确实降到30 cmH20以下的病人，是否应该增加潮气量尚不太清楚，因为缺乏安全阈值的证据，一些专家提出，如果病人感到舒适，气体交换的目标已经达到，则平台压越低越好。
    在实施低牵张通气治疗时还需考虑最佳的Fio2。由于严重低氧血症是 ARDS的一个特征，因此，努力改善氧合状态，使目标动脉血氧饱和度达90％左右，有可能需要高水平的初始Fio2。然而，长时间使用高水平Fio2在理论上可增加氧中毒的危险，后者实际上有可能增加肺实质损害。因此，可能需要采取其他调节手段，在降低Fio2的同时改善氧合状态。方法之一是使用PEEP增加氧合，但实施这种操作时应监测气道平台压。

在ARDSNet临床试验中，两个研究组都根据事先设定的参数(表1)设定了多种Fio2与PEEP值的组合。然而，氧合水平不能很好地预测转归。在 ARDSNet临床试验中，低牵张组的氧合状态较差，尽管该组的死亡率下降。因此，一些专家建议根据肺的力学参数而不是根据气体交换情况来施行PEEP (参见后文)。
    一些替代小潮气量通气的方法要么还没有获得成功(例如部分液体通气法)，要么没有得到证明(例如高频震荡法)。然而，许多没有得到证明的策略，如肺开放(策略)保护性通气或俯卧位，在与小潮气量通气联用时可能有用，因此，这些策略不应被视为互相竞争的疗法。

    不良反应
    小潮气量通气可使二氧化碳分压升高，超过正常范围(许可性高碳酸血症)。正如上面提到的，许可性高碳酸血症可引起呼吸性酸中毒，后者可以通过增加呼吸频率以及肾脏的逐渐缓冲过程得到一定程度的减轻。许可性高碳酸血症的潜在有害影响包括肺血管收缩和肺动脉高压，交感神经系统放电增加产生的促心律失常作用，以及脑血管扩张造成的颅内压升高。然而，实验性资料表明，许可性高碳酸血症不仅安全并且还可能有益。实际上，大多数病例的血流动力学特征因儿茶酚胺释放而得以改善”。但是，对于有心脏病的病人，许可性高碳酸血症很可能应谨慎使用，而颅内压升高则是许可性高碳酸血症的相对禁忌证。
    至少在某些病人中，小潮气量通气与感觉不舒适和难以耐受的呼吸困难相关。对于这种病人可能需要使用大量镇静剂来维持病人—呼吸机同步，虽然在ARDSNet临床试验中，接受小潮气量通气治疗的病人与接受高潮气量通气治疗的病人所需的镇静药剂量相等。如果把不舒适作为一个问题来处理的话，可采取小幅增加潮气量或增加镇静剂的方法。通常可以使用短效制剂如丙泊酚使患者镇静，并且每天间断使用，以确定患者是否需要继续镇静。

不确定领域
    如上所述，通常根据低牵张通气中的Fio2来调整PEEP，正如ARDSNet临床试验中系统定义的那样。这种情况下的高PEEP水平是否有益尚未完全确定。PEEP可防止小气道和肺泡萎陷(指肺塌陷)，进一步改善氧合和通气—灌注的匹配性。高PEEP值也可以减少一种称为”肺不张伤(atelectrauma)”的现象，即肺泡反复开放和萎陷，但主要倾向于萎陷，原因是表面活性物质功能不全引起表面张力升高，或胸腔压力升高促使局部肺区萎陷。评估高PEEP作用的临床研究有关其潜在益处的结果不一致。在床旁，PEEP经常可根据每例病人的治疗反应进行调整。例如，如果在潮气量保持不变时，PEEP增加后平台压没有显著增加，则可以推断为肺 复张。相反，如果平台压的升高等于或大于PEEP的增幅，则提示还没有出现肺复张，并且可能有肺过度膨胀或局部肺过度膨胀。在肺复张的病人中，持续高压充气(指肺复张策略)，随后使用高 PEEP和小潮气量，有可能通过促进肺内充气的均匀分布而减少剪切力所致肺损伤(图3)。但是，这种特指为“肺开放(策略)保护性通气”的方法，尚未在临床试验中得到证明。
    没有急性肺损伤或ARDS的病人出可从减少肺牵张中获益。—些观察性研究的资料支持下述观念：不适当的呼吸机参数可能促进ARDS的发生。即一些病人的ARDS可能是医源性的。另外，由于偶然发生漏诊以及在患者发生急性肺损伤或ARDS后得不到恰当的处理。因此，有入主张对所有接受机械通气治疗(包括围手术期)的病人都要减少肺牵张。但是，至今几乎没有该领域的随机临床试验。

指南
    如上所述，美国胸科医师学会的—次共识会议在1993年建议对ARDS病人采用小潮气量通气治疗。此后，美国胸科医师学会、美国胸科学会或危重医学学会都未再制定有关小潮气量通气的正式指南。但是，所有三个组织都赞同2004年公布的—套称为“脓毒症生存运动”的指南，该指南由厂家赞助。这些指南的制定过程受到批评，尽管其有关机械通气的建议普遍被接受。
    脓毒症生存指南赞同采用小潮气量通气(6ml/kg预计体重)，目标是使吸气末平台压保持在30cmH20以下。这种情况下的高碳酸血症，在病人没有颅内压升高时，确实是可以接受的。 PEEP被建议用来预防呼气末肺泡萎陷和维持充分氧合。
 建议
小病历描述的病人适合采用小潮气量通气治疗，因为病人的诊断是 ARDS，并且采用常规机械通气时的气道平台压高。应该按照ARDSNet公式将潮气量降低到6ml/kg预计体重(对于该病人，计算得出的潮气量是440 ml)。我随后会将通气频率增加到20次/分，并观察由此产生的平台压和动脉血气水平，然后根据需要进行调整。对于平台压高于30cmH20的病人，我将进一步降低潮气量，降幅为1ml/kg预计体重，然后复测平台压。对于动脉血氧饱和度低于88％-90％的病人，我会试行增加PEEP来提高氧合，但平台压不超过目标值，根据每例病人的病情况，我会经常试行肺复张策略(在深度镇静和充分液体复苏的前提下持续高压充气，然后试看通过提高PEEP水中来保持肺复张并观察由此产生的平台压变化。 
   
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