肺梗塞指南

1、2014 ESC Guidelines on the diagnosis andmanagement of acute pulmonary embolism,推薦類別和證據(jù)級別,推薦類別和證據(jù)級別,對推薦類別的表述I類：指那些已證實和(或)一致公認有益、有用和有效的操作或治療，推薦使用。Ⅱ類：指那些有用／有效的證據(jù)尚有矛盾或存在不同觀點的操作或治療。Ⅱa類：有關證據(jù)／觀點傾向于有用／有效，應用這些操作或治療是合理的。Ⅱb類：

2、有關證據(jù)／觀點尚不能充分證明有用／有效，可以考慮應用。Ⅲ類：指那些已證實和(或)一致公認無用和(或)無效，并對一些病例可能有害的操作或治療，不推薦使用。對證據(jù)來源的水平表達如下：證據(jù)水平A：資料來源于多項隨機臨床試驗或薈萃分析。證據(jù)水平B：資料來源于單項隨機臨床試驗或多項非隨機對照研究。證據(jù)水平C：僅為專家共識意見和(或)小規(guī)模研究、回顧性研究、注冊研究。,簡介,基本概念流行病學易患因素自然病程病理生理臨床肺梗塞

3、嚴重分級,基本概念,肺栓塞（pulmonary embolism,PE):是以各種栓子堵塞肺動脈系統(tǒng)為其發(fā)病原因的一組疾病或臨床綜合征的總稱，包括肺血栓栓塞、脂肪栓塞、羊水栓塞、空氣栓塞等。肺血栓栓塞癥（pulmonary thromboembolism, PTE):是指來源于靜脈系統(tǒng)或右心血栓堵塞肺動脈或其分枝引起肺循環(huán)障礙的臨床和病理生理綜合征。肺動脈血栓形成（pulmonary thrombosis）指肺動脈病變基礎上（如肺

4、血管炎、白塞氏病等）原位血栓形成，多見于肺小動脈，并非外周靜脈血栓脫落所致，臨床不易與肺栓塞相鑒別。深靜脈血栓形成（deep venous thrombosis,DVT): 纖維蛋白、血小板、紅細胞等血液成份在深靜脈管腔內形成凝血塊（血栓）。靜脈血栓栓塞癥（venous thrombolism,VTE): PTE 和DVT是同一疾病過程中兩個不同階段， 統(tǒng)稱為VTE.,7,Epidemiology,over 317 000 deat

5、hs were related to VTE in six countries of the European 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 duri

6、ng life 7%of the patients who died early were correctly diagnosed with PE before death. (Cohen AT, Venousthromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Hae

7、most 2007;98(4):756–764.),流行病學,急性PE是VTE最嚴重的臨床表現(xiàn)，多數(shù)情況下PE繼發(fā)于DVT，現(xiàn)有的流行病學多將VTE作為一個整體進行危險因素、自然病程等研究，其年發(fā)病率100-200/10萬人。PE可以沒有癥狀，有時偶然發(fā)現(xiàn)才得以確診，甚至某些PE患者的首發(fā)表現(xiàn)就是猝死，因而很難獲得準確的PE流行病學資料。2004年總人口為4.544億的歐盟6國，與PE有關的死亡超過317,000例。其中，突發(fā)致命性

8、PE占34％，其中死前未能確診的占59％，僅有7％的早期死亡病例在死亡前得以確診。PE的發(fā)生風險與年齡增加相關，40歲以上人群，每增齡10歲PE增加約1倍。,9,Predisposing factors,surgery traumaimmobilizationpregnancyoral contraceptive use hormone replacement therapy cancer obesity infec

9、tion and central venous lines,易患因素,Natural history,The first studies on the natural history of VTE were carried out in the setting of orthopaedic surgery during the 1960s.Registries and hospital discharge datasets of un

10、selected 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 cumulative proportion of patients with e

11、arly 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 a

12、fter discontinuation of anticoa-gulation) has 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 unp

13、rovoked VTE as opposed to the presence of temporary risk factors.Elevated D-dimer levels, either during or after discontinuation of anticoagulation, indicate an increased risk of recurrence.,自然病程,PE/VTE患者30天全因死亡率為9％-11％

14、，3個月全因死亡率為8.6％-17％。VTE存在復發(fā)的風險。VTE早期復發(fā)的累計比例2周時為2.0％，3個月時為6.4％，6個月時為8％。復發(fā)率在前2周最高，隨后逐漸下降，活動期腫瘤和抗凝劑未快速達標是復發(fā)風險增高的獨立預測因素。 VTE晚期復發(fā)（6個月后，多數(shù)在停用抗凝劑后）的累計比例1年時達13％，5年時達23％，10年時達30％。有VTE復發(fā)史的患者更易反復發(fā)作，無明顯誘因的VTE較有暫時性危險因素的VTE更易復發(fā)?？鼓?/p>

15、療期間或停藥后D二聚體水平升高者復發(fā)風險增高。,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

16、pulmonary arterial bed is occluded by thromboemboli.The abrupt increase in pulmonary vascular resistance results in RV dilation, which alters the contractile properties of the RV myocar-dium via the Frank-Starling mecha

17、nism. 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 a reduction of the cardiac output and contribute to s

18、ystemic 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 o

19、f overflow in the capillary bed 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 for

20、amen ovale can be detected by echocardiography,病理生理,1.　血流動力學改變：PE可導致肺循環(huán)阻力增加，肺動脈壓升高。肺血管床面積減少25%～30%時肺動脈平均壓輕度升高，肺血管床面積減少30%～40%時肺動脈平均壓可達30 mm Hg以上，右室平均壓可升高；肺血管床面積減少40%～50%時肺動脈平均壓可達40 mm Hg，右室充盈壓升高，心指數(shù)下降；肺血管床面積減少50%～70

21、%可出現(xiàn)持續(xù)性肺動脈高壓；肺血管床面積減少＞85%可導致猝死。PE時血栓素A2等物質釋放，可誘發(fā)血管收縮。解剖學阻塞和血管收縮導致肺血管阻力增加，動脈順應性下降。,病理生理,2.　右心功能：肺血管阻力突然增加導致右心室壓力和容量增加、右心室擴張，使室壁張力增加、肌纖維拉伸，右心室收縮時間延長；神經(jīng)體液激活導致變力和變時刺激。上述代償機制與體循環(huán)血管收縮共同增加了肺動脈壓力，以增加阻塞肺血管床的血流，由此暫時穩(wěn)定體循環(huán)血壓。

22、但這種即刻的代償程度有限，未預適應的薄壁右心室無法產生40mmHg以上的壓力以抵抗平均肺動脈壓，最終發(fā)生右心功能不全。右室壁張力增加使右冠狀動脈相對供血不足，同時右室心肌氧耗增多，可導致心肌缺血，進一步加重右心功能不全。,病理生理,3.　心室間相互作用：右心室收縮時間延長，室間隔在左心室舒張早期突向左側，右束支傳導阻滯可加重心室間不同步，引起左心室舒張早期充盈受損，右心功能不全導致左心回心血量減少，使心輸出量降低，造成體循環(huán)低血壓

23、和血液動力學不穩(wěn)定。,病理生理,4.　呼吸功能：心輸出量的降低引起混合靜脈血氧飽和度降低。阻塞血管和非阻塞血管毛細血管床的通氣/血流比例失調，導致低氧血癥。由于右心房與左心房之間壓差倒轉，1/3的患者超聲可以檢測到經(jīng)過卵圓孔的右向左分流，引起嚴重的低氧血癥，并增加反常栓塞和卒中的風險。,19,Clinical classification of pulmonaryembolism severity,診斷,臨床表現(xiàn)臨床預測規(guī)則

24、D-dimer測定CTA肺灌注/通氣掃描肺血管造影MRA心臟超聲加壓靜脈超聲診斷策略可疑高危肺梗可疑非高危肺梗,臨床表現(xiàn),Pollack CV, Schreiber D, Goldhaber SZ, Slattery D, Fanikos J, O’Neil BJ,Thompson JR, Hiestand B, Briese BA, Pendleton RC, Miller CD, Kline JA. Clinica

25、l 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 Regi

26、stry). J Am Coll Cardiol 2011;57(6):700–706.,臨床預測規(guī)則,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 clinica

27、l model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost 2000;83(3):416–420.,臨床預測規(guī)則,Le Gal G, Righini M, Roy PM, Sanchez O, Aujesky D, Bou

28、nameaux H, Perrier A. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med 2006;144(3):165–171.,D-dimer測定,A number of D-dimer assays are available.The quantitative enzyme

29、-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.Quantit

30、ative latex-derived assays and a whole-blood agglutination 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

31、 PE-unlikely patients as well as in patients with a low clinical probability.The specificity of D-dimer in suspected PE decreases steadily with age, to almost 10% in patients .80 years.In a recent meta-analysis,age-adj

32、usted cut-off values (age x 10 mg/L above 50 years) allowed increasing specificity from 34–46% while retaining a sensitivity above 97%.,Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D, Forgie M, Kovacs G,W

33、ard 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 a

34、nd d-dimer. Ann Intern Med 2001;135(2):98–107.Di Nisio M, Squizzato A, Rutjes AW, Bu¨ller HR, Zwinderman AH, Bossuyt PM.Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism:a systematic revie

35、w. J Thromb Haemost 2007;5(2):296–304.Righini M, Goehring C, Bounameaux H, Perrier A. Effects of age on the performance of common diagnostic tests for pulmonary embolism. Am J Med 2000;109(5):357–361.Schouten HJ, Geers

36、ing 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:

37、systematic review and meta-analysis. 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

38、 to rule out pulmonary embolism. A systematic review of management outcome studies. Thromb Haemost 2009;101(5):886–892.,D-dimer測定,CTA（Computed tomographic pulmonary angiography）,A negative MDCT is an adequate criterion f

39、or 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 positive predictive value of

40、 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 w

41、ay to diagnose DVT in patients with suspected PE, as it 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 resu

42、lts 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/通氣掃描,In acute PE, ventilation is expected to be normal in hypoperfused segments (mi

43、smatch).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-diagnos

44、tic 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,Kova

45、cs G, Dreyer J, Dennie C, Cartier Y, Barnes D, Burton E, Pleasance S,Skedgel C, O’Rouke K,Wells PS. Computed tomographic pulmonary angiography vs. ventilation-perfusion lung scanning in patients with suspected pulmonary

46、embolism:a randomized controlled trial. JAMA 2007;298(23):2743–2753.Alderson PO. Scintigraphic evaluation of pulmonary embolism. Eur J NuclMed1987;13 Suppl:S6–10.,肺灌注/通氣掃描,肺血管造影,Pulmonary angiography has for decades rem

47、ained the ‘gold standard’for 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 percutaneou

48、s catheter-directed treatment 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 complicatio

49、ns in 5%.,van Beek EJ, Reekers JA, Batchelor DA, Brandjes DP, Bu¨ller HR. Feasibility, safety and clinical utility of angiography in patients with suspected pulmonary embolism.Eur Radiol 1996;6(4):415–419.Stein PD,

50、 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):462–468.,MRA,this techniq

51、ue, 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 hypothesis—that a negative MRA com

52、bined with the absence of proximal DVT on CUS may safely rule out clinically significant PE—is being tested in a multicentre outcome study (ClinicalTrials.gov NCT 02059551).,Revel MP, Sanchez O, Couchon S, Planquette B,

53、Hernigou A, Niarra R, Meyer G,Chatellier G. Diagnostic accuracy of magnetic resonance imaging for an acute pulmonary embolism: results of the ‘IRM-EP’ study. J Thromb Haemost 2012;10(5):743–750.Stein PD, Chenevert TL, F

54、owler 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:

55、a multicenter prospective study (PIOPEDIII). Ann Intern Med 2010;152(7):434–3.,心臟超聲,Acute PEmay lead to RV pressure overload and dysfunction,which can be detected by echocardiography.RV dilation is found in at least 25%

56、 of patients with PE, and its detection,either by echocardiography or CT, is useful for risk stratificationof the disease.Echocardiographic findings—based either on a disturbed RV ejection pattern (so-called ‘60–60 sign

57、’) 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 of pre-existing cardiorespiratory disease.175

58、Echocardiographic 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, in

59、which the absence of echocardiographic signs of RV overload or dysfunction practically excludes PE as the cause of haemodynamic instability.Conversely, in a haemodynamically compromised patient with suspected PE, unequi

60、vocal signs of RV pressure overload and dysfunction justify emergency reperfusion treatment for PE if immediate CT angiography is not feasible.182,心臟超聲,Mobile right heart thrombi are detected by transthoracic or transoes

61、ophageal 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, transoesophageal echocardiograp

62、hy 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

63、bilateral central pulmonary emboli in most of these cases.190,加壓靜脈超聲,In the majority of cases, PE originates from DVT in a lower limb.Nowadays, lower limbCUShas largely replaced venography for diagnosing DVT.In the set

64、ting of suspected PE, CUS can be limited to a simple fourpoint examination (groin and popliteal fossa).The probability of a positive proximal CUS in suspected PE is higher in patients with signs and symptoms related to

65、the leg veins than in asymptomatic patients.,臨床預測規(guī)則,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 clinica

66、l model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost 2000;83(3):416–420.,臨床預測規(guī)則,Le Gal G, Righini M, Roy PM, Sanchez O, Aujesky D, Bou

67、nameaux H, Perrier A. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med 2006;144(3):165–171.,診斷策略,診斷策略,Areas of uncertainty,The diagnostic value and clinical significa

68、nce 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, although CT detected PE more frequently than V/Q scanning

69、, 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