肺栓塞的診斷與治療09課件

1、彭文鴻 解放軍306醫(yī)院呼吸內(nèi)科急性肺栓塞（PE）診治進(jìn)展基本概念肺栓塞（pulmonary embolism,PE):是以各種栓子堵塞肺動(dòng)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(dòng)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(dòng)脈血栓形成（pulmonary thrombosis）指肺動(dòng)脈病變基礎(chǔ)上（如肺血管炎、白塞氏病等）原位血栓形成，多見于肺小動(dòng)脈，并非外周靜脈血栓脫落所致，臨床不易與肺栓塞相鑒別。基本概念深靜脈血栓形

2、成（deep venous thrombosis,DVT): 纖維蛋白、血小板、紅細(xì)胞等血液成份在深靜脈管腔內(nèi)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(gè)不同階段， 統(tǒng)稱為VTE.從PTE到VTEPTE: pulmonary thromboembolism 肺血栓栓塞癥DVT: deep venous thrombosis 深靜脈血栓形成VTE: venous thromboembolism 靜脈血栓栓塞癥 VTE = PTE + DVT 強(qiáng)調(diào)VTE觀 概念的轉(zhuǎn)變與防治策略的選擇The incidence of ph

3、ysical signs96% have tachypnea (respiratory rate 16/min) 58% develop rales 53% have an accentuated second heart sound 44% have tachycardia (heart rate 100/min) 43% have fever (temperature 37.8C) 36% have diaphoresis 34% have an S 3 or S 4 gallop 32% have clinical signs and symptoms suggesting thromb

4、ophlebitis 24% have lower extremity edema 23% have a cardiac murmur 19% have cyanosisRevised Geneva ScoreAge 65 years or over (1 point)Previous DVT or PE (3 points)Surgery or fracture within 1 month (2 points)Active malignant condition (2 points)Unilateral lower limb pain (3 points)Haemoptysis (2 po

5、ints)Heart rate:75 to 94 beats per minute (3 points) 95 or more beats per minute (5 points) Pain on deep palpation of lower limb and unilateral oedema (4 points)Revised Geneva Score interpretationThe score obtained relates to probability of PE:0 - 3 points indicates low probability (8%) 4 - 10 point

6、s indicates intermediate probability (28%) 11 points or more indicates high probability (74%) The probabilities derived from the scoring systems can be used to determine the need for, and nature of, further investigations such as D-dimer, ventilation/perfusion scanning and CT pulmonary angiography t

7、o confirm or refute the diagnosis of PE.Simplified Geneva ScoreAge 65 years or over (1 point) Previous DVT or PE (1 point) General anesthesia or fracture within 1 month (1 point) Active malignant condition or malignant condition that has been cured within 1 year (1 point) Unilateral lower limb pain

8、(1 point) Hemoptysis (1 points) Pain on deep palpation of lower limb and unilateral edema (1 point) Heart rate of: 75 to 94 (1 point) Heart rate of: Greater than 94 (1 point) Patients with a score of 2 or less are considered unlikely to have a current PE. Authors suggest that the likelihood of patie

9、nts having a PE with a simplified Geneva score less than 2 and a normal D-Dimer is 3 percent.The Wells scoreclinically suspected DVT - 3.0 points alternative diagnosis is less likely than PE - 3.0 points tachycardia - 1.5 points immobilization/surgery in previous four weeks - 1.5 points history of D

10、VT or PE - 1.5 points hemoptysis - 1.0 points malignancy (treatment for within 6 months, palliative) - 1.0 points Traditional interpretationScore 6.0 - High (probability 59% based on pooled data) Score 2.0 to 6.0 - Moderate (probability 29% based on pooled data) Score 4 - PE likely. Consider diagnos

11、tic imaging. Score 4 or less - PE unlikely. Consider D-dimer to rule out PE. Wells Score for DVTVariable Score Active cancer 1 point Paralysis, paresis, or recent plaster immobilization of the lower extremity 1 point Recently bedridden for more than three days or major surgery within four weeks 1 po

12、int Localized tenderness along the distribution of the deep venous system 1 point Entire leg swollen 1 point Calf swelling by more than 3 cm when compared with the asymptomatic leg 1 point Pitting edema - greater in the symptomatic leg 1 point Collateral superficial veins nonvaricose 1 point Alterna

13、tive diagnosis as likely or more possible than that of DVT -2 points 肺栓塞靜脈血栓栓塞癥Venous thromboembolism: DVT & PE深靜脈血栓DVT肺栓塞PTE/lessons/200309-01.aspEmbolus that originated in the femoral vein of the leg, removed from a pulmonary arteryLarge thrombus in the femoral vein of the leg體格檢查一般檢查 低熱，約占43%呼吸頻率

14、增快，約占70%竇速，約占44%紫紺，約占19%多汗，約占11%下肢靜脈紫腫低血壓，少見。提示為大塊PE心血管系統(tǒng)體征主要是急、慢性肺動(dòng)脈高壓和右心功能不全的表現(xiàn)。53%有肺動(dòng)脈第二音亢進(jìn)。可出現(xiàn)頸靜脈充盈，搏動(dòng)增強(qiáng)，是PE重要的體征，也是右心功能改變的重要窗口。呼吸系統(tǒng)體征 氣管移向患側(cè)隔肌上移病變部位叩診濁音肺野可聞及干濕羅音血漿D-二聚體的應(yīng)用凝血激活凝血酶血凝固 纖維蛋白纖維蛋白原纖維蛋白酶血纖維蛋白溶解纖維蛋白原降解產(chǎn)物包括 D-二聚體 D-二聚體血漿D-二聚體的應(yīng)用D-Dimer的排除診斷價(jià)值血漿D-二聚體檢查 小于500g/L，有排除診斷的價(jià)值。PULMONARY EMBOLIS

15、MDIAGNOSISEKGThe classic findings of right heart strain and acute cor pulmonale are tall, peaked P-waves in lead II (P-pulmonale), right axis deviation, right bundle branch block, an S1-Q3-T3 pattern or atrial fibrillationOnly 20% of patients with proven PE have any of these classic ECG abnormalitie

16、sPULMONARY EMBOLISMDIAGNOSISEKG with S1-Q3-T3血?dú)夥治鯞LOOD GAS低氧血癥、低碳酸血癥、PA-aO2 增大。部分患者的血?dú)庹！７窝艽捕氯?5%20%即可出現(xiàn)氧分壓下降。外周血管超聲檢查探測到較大的下肢深靜脈血栓作為臨床DVT患者的最初檢查減少對肺部影像學(xué)檢查的需要Venous UltrasonographyRelies on loss of vein compressibility as the primary criterionAbout 1/3 of pts will have no imaging evidence of DVTClo

17、t may have already embolizedClot present in the pelvic veins (U/S usually inadequate)Workup for PE should continue even if dopplers (-) in a pt in which you have a high clinical suspicion放射性核素肺通氣/灌注掃描 作為疑有PE患者的標(biāo)準(zhǔn)篩選檢查，其特異性有一定的限度，可有假陽性。螺旋CT血管造影術(shù) 特別是電子束CT，可以直接看到肺動(dòng)脈內(nèi)的血栓。表現(xiàn)為血管內(nèi)的低密度充盈缺損。可清晰地探測位于主、葉及段肺動(dòng)脈內(nèi)的

18、栓子。對于在亞段及一些遠(yuǎn)端肺動(dòng)脈內(nèi)的栓子，SCT的敏感性是有限的。SCT敏感性為53%89%，特異性為78%100%。直接征象有：半月形或環(huán)形充盈缺損，完全梗阻，軌道征等；間接片象有：主肺動(dòng)脈及左右肺動(dòng)脈擴(kuò)張，血管斷面細(xì)小、缺支、馬賽克片、肺梗死灶、胸膜改變等。X線胸片斑片狀浸潤、肺不張、膈肌抬高、胸腔積液、尤其以胸膜為基底凸面朝向肺門的圓形致密陰影（Hampton征），以及擴(kuò)張的肺動(dòng)脈伴遠(yuǎn)端肺紋理稀疏（Westermark征）對PTE診斷有重要價(jià)值，但不特異。CXRInitial CXR usually normal.May progress to show atelectasis, plu

19、eral effusion and elevated hemidiaphram.Hamptons hump and Westermark sign are classic findings but are not usually present.PULMONARY EMBOLISMDIAGNOSISChest X-ray: virtually always normalmay show Westermarks sign, a dilatation of the pulmonary vessels proximal to an embolism, sometimes with a sharp c

20、utoffrare late finding is Hamptons hump, a triangular or rounded pleural-based infiltrate with the apex pointed toward the hilum, frequently located adjacent to the diaphragmChest X-ray findings:Band atelectasis (1 point) Elevation of hemidiaphragm (1 point) The score obtained relates to the probabi

21、lity of the patient having had a pulmonary embolism (the lower the score, the lower the probability):8 points indicates a high probability of PE Hampton hump sign: Refers to a homogeneous wedge-shaped consolidation in the lung periphery with a base contiguous to a visceral pleural surface and a roun

22、ded convex apex directed toward the hilum; associated with pulmonary infarctWestermark sign: Refers to an area of o!igemia with minimal change in lung volume distal to a large PE; this regional oligemia is caused either by mechanical obstruction to blood flow by the clot or by reflex vasoconstrictio

23、nRadiographic Eponyms- Hamptons Hump, Westermarks Sign Westermarks SignHamptons HumpCXRHamptons Hump consists of a pleura based shallow wedge-shaped consolidation in the lung periphery with the base against the pleural surface.PULMONARY EMBOLISMDIAGNOSISWestermarks SignPULMONARY EMBOLISMDIAGNOSISHam

24、ptons HumpPE with hemorrhage or pulmonary edemaPE with effusionand elevated diaphragmV/Q ScanVentilation-perfusion scanning is a radiological procedure which is often used to confirm or exclude the diagnosis of pulmonary embolism. It may also be used to monitor treatment.Ventilation (V) Achieved by

25、the inhalation of Technetium DTPA. DTPA is an elongated version of EDTA and is a heavy metal chelator. Ventilation is assessed under a gamma camera.Perfusion (Q) Achieved by injecting the patient with Technetium 99m, which is coupled with macro aggregated albumin (MAA). An embolus shows up as a cold

26、 area when the patient is placed under a gamma camera.Abnormal V/Q ScanAbnormal V/Q ScanPerfusionVentilationV/Q Scan ResultsClinical probability of emboliScan CategoryHighIntermediateLowHigh958656Intermediate662815Low40154Normal or near normal062Likelihood of pulmonary embolism according to scan cat

27、egory and clinical probability in PIOPED study Spiral CTSpiral CT first introduced in 1990sIn older CT scanners, the X-ray source would move in a circular fashion to acquire a single slice. Once the slice had been completed, the scanner table would move to position the patient for the next slice.In

28、helical CT the X-ray source and detectors are attached to a freely rotating gantry. During a scan, the table moves the patient smoothly through the scanner. The name derives from the helical or spiral path traced out by the X-ray beam.Spiral CTMajor advantage of Spiral CT is speed:Often the patient

29、can hold their breath for the entire study, reducing motion artifacts.Allows for more optimal use of intravenous contrast enhancement.Spiral CT is quicker than the equivalent conventional CT permitting the use of higher resolution acquisitions in the same study time.Contraindicated in cases of renal

30、 disease.Sensitive for PE in the proximal pulmonary arteries, but less so in the distal segments.CT AngiogramQuickly becoming the test of choice for initial evaluation of a suspected PE.CT unlikely to miss any lesion.CT has better sensitivity, specificity and can be used directly to screen for PE.CT

31、 can be used to follow up “non diagnostic V/Q scans.CT AngiogramChest computed tomography scanning demonstrating extensive embolization of the pulmonary arteries.DiagnosisSpiral CT/ Multislice Ascending AortaLt Pulmonary ArteryMain Pulmonary ArteryRt Pulmonary ArteryDescending AortaThrombusPulmonary

32、 embolismThis 62 y/o female presented with shortness of breath and an abnormal chest x-ray. A Spiral CT of the chest with IV contrast was performed. A filling defect in the right pulmonary artery consistent with a pulmonary embolus is demonstrated. CT肺動(dòng)脈造影（CTPA）被廣泛應(yīng)用，可以安排急診檢查能準(zhǔn)確地顯示近端血栓和急性右心室擴(kuò)張可以做定量分

33、析，分析結(jié)果與臨床嚴(yán)重程度的相關(guān)性直接顯示血管內(nèi)血栓，間接顯示繼發(fā)效應(yīng)，楔形陰影或特征性的右心室改變當(dāng)排除PTE時(shí)可能做出其它的正確診斷高質(zhì)量CTPA檢查陰性不進(jìn)行抗凝治療是安全的CT pulmonary angiography (CTPA) showing a saddle embolus and substantial thrombus burden in the lobar branches of both main pulmonary arteries.CT pulmonary angiography (CTPA) showing a saddle embolus and substa

34、ntial thrombus burden in the lobar branches of both main pulmonary arteries. Asian/Pacific Islanders (12.1M)450 - 600,000 episodes/year in USStein et al: Regional Differences in Rates of Diagnosis and Mortality of Pulmonary Thromboembolism; AJC 2004;93:1194-11972008年ESC新版指南取消臨床分型，代之以危險(xiǎn)分層。原因：急性肺栓塞嚴(yán)重程

35、度與肺動(dòng)脈內(nèi)血栓的形態(tài)、分布和血栓量的多少不呈平行關(guān)系。急性肺栓塞的嚴(yán)重程度與急性肺栓塞早期（住院或發(fā)病后30天）死亡危險(xiǎn)程度密切相關(guān)。2008年急性肺栓塞危險(xiǎn)分層的主要指標(biāo)臨床特征休克 低血壓a右心室功能不全 超聲心動(dòng)圖示右心擴(kuò)大運(yùn)動(dòng)減弱或壓力負(fù)荷過重表現(xiàn)螺旋CT示右心擴(kuò)大 BNP或NT-proBNP升高 右心導(dǎo)管術(shù)示右心室壓力增大心肌損傷標(biāo)志物 心臟肌鈣蛋白T或I陽性a：低血壓定義：收縮壓40mmHg達(dá)15分鐘以上，除外新出現(xiàn)的心律失常、低血容量或敗血癥所致低血壓。2008年急性肺栓塞危險(xiǎn)分層早期死亡風(fēng)險(xiǎn)危險(xiǎn)分層指標(biāo)推薦治療 臨床表現(xiàn)右心室功能不全心肌損傷 （休克或低血壓）高危+ a a

36、溶栓或栓子切除術(shù)(15%) 中危 + + (3-15) + 住院治療 + 低危 (180 mmHg) 晚期肝病 感染性心內(nèi)膜炎 活動(dòng)性消化性潰瘍抗凝治療急性肺栓塞初始抗凝治療的目的是減少死亡及再發(fā)栓塞事件。急性肺栓塞患者長期抗凝治療的目的是預(yù)防致死性及非致死性靜脈血栓栓塞事件?？鼓委煈岩杉毙苑嗡ㄈ幕颊叩却M(jìn)一步確診過程中即應(yīng)開始抗凝治療。高?；颊呷芩ê笮蜇灴鼓委煛Ｖ小⒌臀；颊呖鼓委熓腔镜闹委煷胧３Ｓ玫目鼓幬锓强诜鼓帲浩胀ǜ嗡?、低分子量肝素、磺達(dá)肝素口服抗凝藥：華法林、利伐沙班（近期上市）。阿司匹林和波立維不推薦應(yīng)用于治療靜脈血栓。抗凝治療普通肝素應(yīng)用指征血流動(dòng)力學(xué)不穩(wěn)定的高危

37、肺栓塞患者（因?yàn)槟壳耙恍┍容^普通肝素和低分子量肝素的抗凝效果和安全性的臨床試驗(yàn)中并不包括這些高危患者）。 腎功能不全患者（因普通肝素經(jīng)網(wǎng)狀內(nèi)皮系統(tǒng)清除，不經(jīng)腎臟代謝）。高出血風(fēng)險(xiǎn)患者（因普通肝素抗凝作用可迅速被中和）。對其他急性肺栓塞患者，低分子量肝素可替代普通肝素。磺達(dá)肝癸鈉與低分子量肝素具有同樣的抗凝效果,且無需監(jiān)測。 抗凝治療 常用的普通肝素給藥方法是靜脈滴注，首劑負(fù)荷量為80U/kg（一般30005000U)，繼之7001 000U/h或18U/kg/h維持。用普通肝素治療需要監(jiān)測激活的部分凝血活酶時(shí)間（APTT）,APTT至少要大于對照值的1.5倍（通常是1.5倍2.0倍）。 根據(jù)體

38、重調(diào)整普通肝素用量的“Raschke”方案 APTT 肝素劑量的調(diào)節(jié) 秒 控制倍數(shù) 首劑負(fù)荷量80IU/kg, 隨后18IU/(kg.h)維持 35 90 3.0 停藥1h,隨后減量 3IU/(kg.h)繼續(xù)給藥低分子量肝素和磺達(dá)肝癸鈉給藥方案藥物劑量間隔時(shí)間Enoxaparin 1.0 mg/kg 每12 h一次（克賽）or 1.5 mg/kg 每天一次Tinzaparin 175 U/kg 每天一次（亭扎肝素）Fondaparinux 5 mg (體重50 kg)每天一次（磺達(dá)肝素）7.5 mg (體重50100 kg)10 mg (體重100 kg)抗凝治療 肝素需與華法林重疊使用，直到

39、INR達(dá)標(biāo)（2.03.0）2天后再停用肝素。最常用口服藥物為華法林，初期應(yīng)與肝素重疊使用，對于年輕（小于60歲）患者或者既往健康的院外患者而言，起始劑量通常為10mg；而對于老年及住院患者，起始劑量通常為5mg，以后根據(jù)國際標(biāo)準(zhǔn)化比值（INR）調(diào)整劑量,長期服用者INR宜維持在2.03.0之間?？鼓委煏r(shí)程急性肺栓塞的抗凝時(shí)間長短應(yīng)個(gè)體化，一般至少需要3個(gè)月。如果急性肺栓塞（0.55患者）發(fā)展成慢性血栓栓塞性肺動(dòng)脈高壓者應(yīng)長期抗凝治療。如果急性肺栓塞治療成功，癥狀基本消失，無右心壓力負(fù)荷，影像學(xué)檢查肺栓塞基本消失者應(yīng)根據(jù)血栓形成的誘發(fā)因素類型決定抗凝時(shí)程?？鼓委煏r(shí)程由暫時(shí)或可逆性誘發(fā)因素（服

40、用雌激素、臨時(shí)制動(dòng)、創(chuàng)傷和手術(shù)）導(dǎo)致的肺栓塞患者推薦抗凝時(shí)程為3個(gè)月。對于無明顯誘發(fā)因素的首次肺栓塞患者（特發(fā)性靜脈血栓）建議抗凝至少3個(gè)月，3個(gè)月后評估出血和獲益風(fēng)險(xiǎn)再?zèng)Q定是否長期抗凝治療，對于無出血風(fēng)險(xiǎn)且方便進(jìn)行抗凝監(jiān)測的患者建議長期抗凝治療。對于再次發(fā)生的無誘發(fā)因素的肺栓塞患者建議長期抗凝。對于靜脈血栓栓塞危險(xiǎn)因素長期存在的患者應(yīng)長期抗凝治療，如癌癥患者、抗心脂抗體綜合征、易栓癥等。可疑患者體征、心電圖、超聲心動(dòng)圖、D-二聚體、血?dú)夥治?、心肌?高度可疑即可抗凝治療 肺動(dòng)脈增強(qiáng)CT或核素肺灌注危險(xiǎn)分層（血壓、右心負(fù)荷、心肌酶）高危中危低危 溶栓 抗凝 院外抗凝急性肺栓塞診治流程下腔靜脈濾

41、器植入適應(yīng)證肺栓塞合并抗凝治療禁忌或抗凝治療出現(xiàn)并發(fā)癥者充分抗凝治療后肺栓塞復(fù)發(fā)者高危患者的預(yù)防：廣泛、進(jìn)行性靜脈血栓形成；行導(dǎo)管介入治療或肺動(dòng)脈血栓剝脫術(shù)者；嚴(yán)重肺動(dòng)脈高壓或肺心病者。 因?yàn)V器只能預(yù)防肺栓塞復(fù)發(fā)，并不能治療DVT，因此安裝濾器后如無抗凝禁忌仍需抗凝，防止進(jìn)一步血栓形成。預(yù)防機(jī)械性措施可計(jì)量壓力的彈力襪（ES）間斷充分壓迫裝置（ IPC）可促使血管內(nèi)皮纖維蛋白溶解，因此可用于高出血風(fēng)險(xiǎn)患者或作為在藥物抗凝基礎(chǔ)上的輔助預(yù)防措施。小劑量肝素（ LDUH）聯(lián)合ES、IPC組更有效Kamran SI, Downey D, Ruff RL, Pneumatic sequential co

42、mpression reduces the risk of deep rein thrombosis in stroke patients. Neurology, 1998,50:1683-1688. 藥物預(yù)防（1）預(yù)防應(yīng)以抗凝血酶藥物為主，不主張單獨(dú)阿司匹林預(yù)防。LMWH的安全性好，其預(yù)防效果與UFH5000IU，2次/d相似。對有危險(xiǎn)因素的小手術(shù)、年齡40-60歲或有危險(xiǎn)因素的非大型手術(shù)的中度危險(xiǎn)患者，推薦使用UFH5000IU，2次/d或LMWH3400IU/d。對年齡大于60歲或有危險(xiǎn)因素的非大型手術(shù)患者，年齡大于40歲或有危險(xiǎn)因素需大型手術(shù)的高?；颊?，推薦使用UFH5 000IU，3

43、次/d或LMWH3 400IU/d。藥物預(yù)防（2）對有多種危險(xiǎn)因素的極高?；颊撸扑]選用戊聚糖鈉、LMWH或維生素K拮抗劑，預(yù)防用藥至少10d。大多數(shù)ICU患者都需要使用LDUH或LMWH進(jìn)行預(yù)防性抗凝。ACCP-7首次公布對長途旅行者靜脈血栓栓塞癥預(yù)防的建議：如果飛行時(shí)間超過6h，無論有無PTE-DVT危險(xiǎn)因素，旅行者都應(yīng)該進(jìn)行腓腸肌仲縮、避免穿使下肢和腰部緊身的衣褲、避免脫水，對有PTE-DVT危險(xiǎn)因素者應(yīng)考慮使用ES或旅行前皮下注射一劑LMWH。靜脈血栓栓塞的預(yù)防不再推薦的抗凝藥物包括：達(dá)那肝素（danaparoid）、重組水蛭素和低分子右旋糖酐等，也不主張采用調(diào)整劑量的UFH進(jìn)行預(yù)防性

44、抗凝治療。靜脈血栓栓塞癥VTE = Deep Vein Thrombosis (DVT) +Pulmonary Embolism (PE)Thrombus in oneof the deep veinsEmbolusPerfusion defectVTE是沉寂的“殺手”!第3位最常見的血管疾病Symptomatic VTE AsymptomaticVTE/site/Alaska.phpOver 70% PEare detected“POSMORTEM”Between 50%- 80% of DVTs are clinically silent(Stein,1995), (Lethen, 1997)深靜脈血栓臨床癥狀 DVT可以無癥狀，