1、2014 ESC Guidelines on the diagnosis andmanagement of acute pulmonary embolism,推荐类别和证据级别,推荐类别和证据级别,对推荐类别的表述I类：指那些已证实和(或)一致公认有益、有用和有效的操作或治疗，推荐使用。类：指那些有用有效的证据尚有矛盾或存在不同观点的操作或治疗。a类：有关证据观点倾向于有用有效，应用这些操作或治疗是合理的。b类：有关证据观点尚不能充分证明有用有效，可以考虑应用。类：指那些已证实和(或)一致公认无用和(或)无效，并对一些病例可能有害的操作或治疗，不推荐使用。对证据来源的水平表达如下：证据水平A：
2、资料来源于多项随机临床试验或荟萃分析。证据水平B：资料来源于单项随机临床试验或多项非随机对照研究。证据水平C：仅为专家共识意见和(或)小规模研究、回顾性研究、注册研究。,简介,基本概念流行病学易患因素自然病程病理生理临床肺梗塞严重分级,基本概念,肺栓塞（pulmonary embolism,PE):是以各种栓子堵塞肺动脉系统为其发病原因的一组疾病或临床综合征的总称，包括肺血栓栓塞、脂肪栓塞、羊水栓塞、空气栓塞等。肺血栓栓塞症（pulmonary thromboembolism, PTE):是指来源于静脉系统或右心血栓堵塞肺动脉或其分枝引起肺循环障碍的临床和病理生理综合征。肺动脉血栓形成（pul
3、monary thrombosis）指肺动脉病变基础上（如肺血管炎、白塞氏病等）原位血栓形成，多见于肺小动脉，并非外周静脉血栓脱落所致，临床不易与肺栓塞相鉴别。深静脉血栓形成（deep venous thrombosis,DVT): 纤维蛋白、血小板、红细胞等血液成份在深静脉管腔内形成凝血块（血栓）。静脉血栓栓塞症（venous thrombolism,VTE): PTE 和DVT是同一疾病过程中两个不同阶段， 统称为VTE.,7,Epidemiology,over 317 000 deaths were related to VTE in six countries of the Europ
4、ean Union (with a total population of 454.4 million) in 2004: 34% presented with sudden fatal PE 59% were deaths resulting from PE that remained undiagnosed during life 7%of the patients who died early were correctly diagnosed with PE before death. (Cohen AT, Venousthromboembolism (VTE) in Europe. T
5、he number of VTE events and associated morbidity and mortality. Thromb Haemost 2007;98(4):756764.),流行病学,急性PE是VTE最严重的临床表现，多数情况下PE继发于DVT，现有的流行病学多将VTE作为一个整体进行危险因素、自然病程等研究，其年发病率100-200/10万人。PE可以没有症状，有时偶然发现才得以确诊，甚至某些PE患者的首发表现就是猝死，因而很难获得准确的PE流行病学资料。2004年总人口为4.544亿的欧盟6国，与PE有关的死亡超过317,000例。其中，突发致命性PE占34，其中死
6、前未能确诊的占59，仅有7的早期死亡病例在死亡前得以确诊。PE的发生风险与年龄增加相关，40岁以上人群，每增龄10岁PE增加约1倍。,9,Predisposing factors,surgery traumaimmobilizationpregnancyoral contraceptive use hormone replacement therapy cancer obesity infection and central venous lines,易患因素,Natural history,The first studies on the natural history of VTE wer
7、e carried out in the setting of orthopaedic surgery during the 1960s.Registries and hospital discharge datasets of unselected patients with PE or VTE yielded 30-day all-cause mortality rates between 9% and 11%, and three-month mortality ranging between 8.6% and 17%.Based on historical data, the cumu
8、lative proportion of patients with early recurrence of VTE (on anticoagulant treatment) amounts to 2.0% at 2 weeks, 6.4% at 3 months and 8% at 6 months.The cumulative proportion of patients with late recurrence of VTE(after six months, and in most cases after discontinuation of anticoa-gulation) has
9、 been reported to reach 13% at 1 year, 23% at 5 years,and 30% at 10 years.Recurrence is more frequent after multiple VTE epi-sodes as opposed to a single event, and after unprovoked VTE as opposed to the presence of temporary risk factors.Elevated D-dimer levels, either during or after discontinuati
10、on of anticoagulation, indicate an increased risk of recurrence.,自然病程,PE/VTE患者30天全因死亡率为9-11，3个月全因死亡率为8.6-17。VTE存在复发的风险。VTE早期复发的累计比例2周时为2.0，3个月时为6.4，6个月时为8。复发率在前2周最高，随后逐渐下降，活动期肿瘤和抗凝剂未快速达标是复发风险增高的独立预测因素。 VTE晚期复发（6个月后，多数在停用抗凝剂后）的累计比例1年时达13，5年时达23，10年时达30。有VTE复发史的患者更易反复发作，无明显诱因的VTE较有暂时性危险因素的VTE更易复发。抗凝治疗
11、期间或停药后D二聚体水平升高者复发风险增高。,Pathophysiology,Acute PE interferes with both the circulation and gas exchange.CIRCULATIONPulmonary artery pressure increases only if more than 30 50% of the total cross-sectional area of the pulmonary arterial bed is occluded by thromboemboli.The abrupt increase in pulmonary
12、vascular resistance results in RV dilation, which alters the contractile properties of the RV myocar-dium via the Frank-Starling mechanism. The prolongation of RV contraction time into early diastole in the left ventricle leads to leftward bowing of the interventricular septum. And this may lead to
13、a reduction of the cardiac output and contribute to systemic hypotension and haemodynamic instability.RESPIRATORY FAILURELow cardiac output results in desat-uration of the mixed venous blood. In addition, zones of reduced flow in obstructed vessels, combined with zones of overflow in the capillary b
14、ed served by non-obstructed vessels, result in ventila-tion perfusion mismatch, which contributes to hypoxaemia. In about one-third of patients, right-to-left shunting through a patent foramen ovale can be detected by echocardiography,病理生理,1.血流动力学改变：PE可导致肺循环阻力增加，肺动脉压升高。肺血管床面积减少25%30%时肺动脉平均压轻度升高，肺血管床
15、面积减少30%40%时肺动脉平均压可达30 mm Hg以上，右室平均压可升高；肺血管床面积减少40%50%时肺动脉平均压可达40 mm Hg，右室充盈压升高，心指数下降；肺血管床面积减少50%70%可出现持续性肺动脉高压；肺血管床面积减少85%可导致猝死。PE时血栓素A2等物质释放，可诱发血管收缩。解剖学阻塞和血管收缩导致肺血管阻力增加，动脉顺应性下降。,病理生理,2.右心功能：肺血管阻力突然增加导致右心室压力和容量增加、右心室扩张，使室壁张力增加、肌纤维拉伸，右心室收缩时间延长；神经体液激活导致变力和变时刺激。上述代偿机制与体循环血管收缩共同增加了肺动脉压力，以增加阻塞肺血管床的血流，由此暂
16、时稳定体循环血压。但这种即刻的代偿程度有限，未预适应的薄壁右心室无法产生40mmHg以上的压力以抵抗平均肺动脉压，最终发生右心功能不全。右室壁张力增加使右冠状动脉相对供血不足，同时右室心肌氧耗增多，可导致心肌缺血，进一步加重右心功能不全。,病理生理,3.心室间相互作用：右心室收缩时间延长，室间隔在左心室舒张早期突向左侧，右束支传导阻滞可加重心室间不同步，引起左心室舒张早期充盈受损，右心功能不全导致左心回心血量减少，使心输出量降低，造成体循环低血压和血液动力学不稳定。,病理生理,4.呼吸功能：心输出量的降低引起混合静脉血氧饱和度降低。阻塞血管和非阻塞血管毛细血管床的通气/血流比例失调，导致低氧血
17、症。由于右心房与左心房之间压差倒转，1/3的患者超声可以检测到经过卵圆孔的右向左分流，引起严重的低氧血症，并增加反常栓塞和卒中的风险。,19,Clinical classification of pulmonaryembolism severity,诊断,临床表现临床预测规则D-dimer测定CTA肺灌注/通气扫描肺血管造影MRA心脏超声加压静脉超声诊断策略可疑高危肺梗可疑非高危肺梗,临床表现,Pollack CV, Schreiber D, Goldhaber SZ, Slattery D, Fanikos J, ONeil BJ,Thompson JR, Hiestand B, Bries
18、e BA, Pendleton RC, Miller CD, Kline JA. Clinical characteristics, management, and outcomes of patients diagnosed with acute pulmonary embolism in the emergency department: initial report ofEMPEROR(Multicenter Emergency Medicine PulmonaryEmbolism in the RealWorld Registry). J Am Coll Cardiol 2011;57
19、(6):700706.,临床预测规则,Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M, Turpie AG,Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRE
20、D D-dimer. Thromb Haemost 2000;83(3):416420.,临床预测规则,Le Gal G, Righini M, Roy PM, Sanchez O, Aujesky D, Bounameaux H, Perrier A. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med 2006;144(3):165171.,D-dimer测定,A number of D-dimer assays are availabl
21、e.The quantitative enzyme-linked immunosorbent assay (ELISA) or ELISA-derived assays have a diagnostic sensitivity of 95% or better and can therefore be used to exclude PE in patients with either a low or a moderate pre-test probability.Quantitative latex-derived assays and a whole-blood agglutinati
22、on assay have a diagnostic sensitivity ,95% and are thus often referred to as moderately sensitive. In outcome studies, those assays proved safe in ruling out PE in PE-unlikely patients as well as in patients with a low clinical probability.The specificity of D-dimer in suspected PE decreases steadi
23、ly with age, to almost 10% in patients .80 years.In a recent meta-analysis,age-adjusted cut-off values (age x 10 mg/L above 50 years) allowed increasing specificity from 3446% while retaining a sensitivity above 97%.,Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D, Forgie M, Kovacs G,
24、Ward J, Kovacs MJ. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. Ann Intern Med 2001;135(2):98107.Di Nisio M, Squizzato A, Rutjes AW
25、, Buller HR, Zwinderman AH, Bossuyt PM.Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism:a systematic review. J Thromb Haemost 2007;5(2):296304.Righini M, Goehring C, Bounameaux H, Perrier A. Effects of age on the performance of common diagnostic tests for pulmonary embolis
26、m. Am J Med 2000;109(5):357361.Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA, van Delden JJ, Moons KG, Reitsma JB. Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism:systematic review and meta-anal
27、ysis. BMJ 2013;346:f2492.,Carrier M, Righini M, Djurabi RK, Huisman MV, Perrier A, Wells PS, Rodger M,Wuillemin WA, Le Gal G. VIDAS D-dimer in combination with clinical pre-test probability to rule out pulmonary embolism. A systematic review of management outcome studies. Thromb Haemost 2009;101(5):
28、886892.,D-dimer测定,CTA（Computed tomographic pulmonary angiography）,A negative MDCT is an adequate criterion for excluding PE in patients with a non-high clinical probability of PE.Whether patients with a negativeCT and a high clinical probability should be further investigated is controversial.The po
29、sitive predictive value of MDCT is lower in patients with a low clinical probability of PE.The clinical significance of isolated sub-segmental PE on CT angiography is questionable.Computed tomographic venography has been advocated as a simple way to diagnose DVT in patients with suspected PE, as it
30、can be combined with chest CT angiography as a single procedure, using only one intravenous injection of contrast dye.As CT venography and CUS yielded similar results in patients with signs or symptoms of DVT in PIOPED II,ultrasonography should be used instead of CT venography if indicated.,CTA,肺灌注/
31、通气扫描,In acute PE, ventilation is expected to be normal in hypoperfused segments (mismatch).145,146Lung scan results are frequently classified : normal scan (excluding PE), highprobability scan (considered diagnostic of PE in most patients), and non-diagnostic scan.135The high frequency of non-diagno
32、stic intermediate probability scans has been a cause for criticism, because they indicate the necessity for further diagnostic testing.,Anderson DR, Kahn SR, Rodger MA, Kovacs MJ, Morris T, Hirsch A, Lang E, Stiell I,Kovacs G, Dreyer J, Dennie C, Cartier Y, Barnes D, Burton E, Pleasance S,Skedgel C,
33、 ORouke K,Wells PS. Computed tomographic pulmonary angiography vs. ventilation-perfusion lung scanning in patients with suspected pulmonary embolism:a randomized controlled trial. JAMA 2007;298(23):27432753.Alderson PO. Scintigraphic evaluation of pulmonary embolism. Eur J NuclMed1987;13 Suppl:S610.
34、,肺灌注/通气扫描,肺血管造影,Pulmonary angiography has for decades remained the gold standardfor the diagnosis or exclusion of PE, but is rarely performed now as less-invasive CT angiography offers similar diagnostic accuracy.Pulmonary angiography is more often used to guide percutaneous catheter-directed treatm
35、ent of acute PE.Pulmonary angiography is not free of risk. In a study of 1111 patients, procedure-related mortality was 0.5%, major non-fatal complications occurred in 1%, and minor complications in 5%.,van Beek EJ, Reekers JA, Batchelor DA, Brandjes DP, Buller HR. Feasibility, safety and clinical u
36、tility of angiography in patients with suspected pulmonary embolism.Eur Radiol 1996;6(4):415419.Stein PD, Athanasoulis C, Alavi A, Greenspan RH, Hales CA, Saltzman HA,Vreim CE, Terrin ML, Weg JG. Complications and validity of pulmonary angiography in acute pulmonary embolism. Circulation 1992;85(2):
37、462468.,MRA,this technique, although promising, is not yet ready for clinical practice due to its low sensitivity,high proportion of inconclusive MRA scans, and low availability in most emergency settings.The hypothesisthat a negative MRA combined with the absence of proximal DVT on CUS may safely r
38、ule out clinically significant PEis being tested in a multicentre outcome study (ClinicalTrials.gov NCT 02059551).,Revel MP, Sanchez O, Couchon S, Planquette B, Hernigou A, Niarra R, Meyer G,Chatellier G. Diagnostic accuracy of magnetic resonance imaging for an acute pulmonary embolism: results of t
39、he IRM-EP study. J Thromb Haemost 2012;10(5):743750.Stein PD, Chenevert TL, Fowler SE, Goodman LR, Gottschalk A, Hales CA,Hull RD, Jablonski KA, Leeper KV Jr., Naidich DP, Sak DJ, Sostman HD,Tapson VF, Weg JG, Woodard PK. Gadolinium-enhanced magnetic resonance angiography for pulmonary embolism: a m
40、ulticenter prospective study (PIOPEDIII). Ann Intern Med 2010;152(7):4343.,心脏超声,Acute PEmay lead to RV pressure overload and dysfunction,which can be detected by echocardiography.RV dilation is found in at least 25% of patients with PE, and its detection,either by echocardiography or CT, is useful f
41、or risk stratificationof the disease.Echocardiographic findingsbased either on a disturbed RV ejection pattern (so-called 6060 sign) or on contractility of the RV free wall compared with the RV apex (McConnell sign)were reported to retain a high positive predictive value for PE, even in the presence
42、 of pre-existing cardiorespiratory disease.175Echocardiographic examination is not recommended as part of the diagnostic work-up in haemodynamically stable, normotensive patients with suspected (not high-risk) PE.157 This is in contrast to suspected high-risk PE, inwhich the absence of echocardiogra
43、phic signs of RV overload or dysfunction practically excludes PE as the cause of haemodynamic instability.Conversely, in a haemodynamically compromised patient with suspected PE, unequivocal signs of RV pressure overload and dysfunction justify emergency reperfusion treatment for PE if immediate CT
44、angiography is not feasible.182,心脏超声,Mobile right heart thrombi are detected by transthoracic or transoesophageal echocardiography (or by CT angiography) in less than 4% of unselected patients with PE,183 185 but their prevalence may reach 18% in the intensive care setting.185Consequently, transoeso
45、phageal echocardiography may be considered when searching for emboli in the main pulmonary arteries in specific clinical situations,188,189 and it can be of diagnostic value in haemodynamically unstable patients due to the high prevalence of bilateral central pulmonary emboli in most of these cases.
46、190,加压静脉超声,In the majority of cases, PE originates from DVT in a lower limb.Nowadays, lower limbCUShas largely replaced venography for diagnosing DVT.In the setting of suspected PE, CUS can be limited to a simple fourpoint examination (groin and popliteal fossa).The probability of a positive proxima
47、l CUS in suspected PE is higher in patients with signs and symptoms related to the leg veins than in asymptomatic patients.,临床预测规则,Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M, Turpie AG,Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J. Derivation of a simple clinical
48、 model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost 2000;83(3):416420.,临床预测规则,Le Gal G, Righini M, Roy PM, Sanchez O, Aujesky D, Bounameaux H, Perrier A. Prediction of pulmonary embolism in the emergency department
49、: the revised Geneva score. Ann Intern Med 2006;144(3):165171.,诊断策略,诊断策略,Areas of uncertainty,The diagnostic value and clinical significance of sub-segmental defects on MDCT are still under debatThere is also growing evidence suggesting over-diagnosis of PE.206 A randomized comparison showed that, a
50、lthough CT detected PE more frequently than V/Q scanning, three-month outcomes were similar, regardless of the diagnostic method used.Some experts believe that patients with incidental (unsuspected) PE on CT should be treated,144 especially if they have cancer and a proximal clot, but solid evidence in support of this recommendation is lacking.,
