肺栓塞的诊断与治疗09课件

1、彭文鸿 解放军306医院呼吸内科急性肺栓塞（PE）诊治进展基本概念肺栓塞（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（pulmonary 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。基本概念深静脉血栓形

2、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.从PTE到VTEPTE: pulmonary thromboembolism 肺血栓栓塞症DVT: deep venous thrombosis 深静脉血栓形成VTE: venous thromboembolism 静脉血栓栓塞症 VTE = PTE + DVT 强调VTE观 概念的转变与防治策略的选择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 肺栓塞静脉血栓栓塞症Venous thromboembolism: DVT & PE深静脉血栓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体格检查一般检查 低热，约占43%呼吸频率

14、增快，约占70%窦速，约占44%紫绀，约占19%多汗，约占11%下肢静脉紫肿低血压，少见。提示为大块PE心血管系统体征主要是急、慢性肺动脉高压和右心功能不全的表现。53%有肺动脉第二音亢进。可出现颈静脉充盈，搏动增强，是PE重要的体征，也是右心功能改变的重要窗口。呼吸系统体征 气管移向患侧隔肌上移病变部位叩诊浊音肺野可闻及干湿罗音血浆D-二聚体的应用凝血激活凝血酶血凝固 纤维蛋白纤维蛋白原纤维蛋白酶血纤维蛋白溶解纤维蛋白原降解产物包括 D-二聚体 D-二聚体血浆D-二聚体的应用D-Dimer的排除诊断价值血浆D-二聚体检查 小于500g/L，有排除诊断的价值。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血气分析BLOOD GAS低氧血症、低碳酸血症、PA-aO2 增大。部分患者的血气正常。肺血管床堵塞15%20%即可出现氧分压下降。外周血管超声检查探测到较大的下肢深静脉血栓作为临床DVT患者的最初检查减少对肺部影像学检查的需要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放射性核素肺通气/灌注扫描 作为疑有PE患者的标准筛选检查，其特异性有一定的限度，可有假阳性。螺旋CT血管造影术 特别是电子束CT，可以直接看到肺动脉内的血栓。表现为血管内的低密度充盈缺损。可清晰地探测位于主、叶及段肺动脉内的

18、栓子。对于在亚段及一些远端肺动脉内的栓子，SCT的敏感性是有限的。SCT敏感性为53%89%，特异性为78%100%。直接征象有：半月形或环形充盈缺损，完全梗阻，轨道征等；间接片象有：主肺动脉及左右肺动脉扩张，血管断面细小、缺支、马赛克片、肺梗死灶、胸膜改变等。X线胸片斑片状浸润、肺不张、膈肌抬高、胸腔积液、尤其以胸膜为基底凸面朝向肺门的圆形致密阴影（Hampton征），以及扩张的肺动脉伴远端肺纹理稀疏（Westermark征）对PTE诊断有重要价值，但不特异。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肺动脉造影（CTPA）被广泛应用，可以安排急诊检查能准确地显示近端血栓和急性右心室扩张可以做定量分

33、析，分析结果与临床严重程度的相关性直接显示血管内血栓，间接显示继发效应，楔形阴影或特征性的右心室改变当排除PTE时可能做出其它的正确诊断高质量CTPA检查阴性不进行抗凝治疗是安全的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新版指南取消临床分型，代之以危险分层。原因：急性肺栓塞严重程

35、度与肺动脉内血栓的形态、分布和血栓量的多少不呈平行关系。急性肺栓塞的严重程度与急性肺栓塞早期（住院或发病后30天）死亡危险程度密切相关。2008年急性肺栓塞危险分层的主要指标临床特征休克 低血压a右心室功能不全 超声心动图示右心扩大运动减弱或压力负荷过重表现螺旋CT示右心扩大 BNP或NT-proBNP升高 右心导管术示右心室压力增大心肌损伤标志物 心脏肌钙蛋白T或I阳性a：低血压定义：收缩压40mmHg达15分钟以上，除外新出现的心律失常、低血容量或败血症所致低血压。2008年急性肺栓塞危险分层早期死亡风险危险分层指标推荐治疗 临床表现右心室功能不全心肌损伤 （休克或低血压）高危+ a a

36、溶栓或栓子切除术(15%) 中危 + + (3-15) + 住院治疗 + 低危 (180 mmHg) 晚期肝病 感染性心内膜炎 活动性消化性溃疡抗凝治疗急性肺栓塞初始抗凝治疗的目的是减少死亡及再发栓塞事件。急性肺栓塞患者长期抗凝治疗的目的是预防致死性及非致死性静脉血栓栓塞事件。抗凝治疗怀疑急性肺栓塞的患者等待进一步确诊过程中即应开始抗凝治疗。高危患者溶栓后序贯抗凝治疗。中、低危患者抗凝治疗是基本的治疗措施。常用的抗凝药物非口服抗凝药：普通肝素、低分子量肝素、磺达肝素口服抗凝药：华法林、利伐沙班（近期上市）。阿司匹林和波立维不推荐应用于治疗静脉血栓。抗凝治疗普通肝素应用指征血流动力学不稳定的高危

37、肺栓塞患者（因为目前一些比较普通肝素和低分子量肝素的抗凝效果和安全性的临床试验中并不包括这些高危患者）。 肾功能不全患者（因普通肝素经网状内皮系统清除，不经肾脏代谢）。高出血风险患者（因普通肝素抗凝作用可迅速被中和）。对其他急性肺栓塞患者，低分子量肝素可替代普通肝素。磺达肝癸钠与低分子量肝素具有同样的抗凝效果,且无需监测。 抗凝治疗 常用的普通肝素给药方法是静脉滴注，首剂负荷量为80U/kg（一般30005000U)，继之7001 000U/h或18U/kg/h维持。用普通肝素治疗需要监测激活的部分凝血活酶时间（APTT）,APTT至少要大于对照值的1.5倍（通常是1.5倍2.0倍）。 根据体

38、重调整普通肝素用量的“Raschke”方案 APTT 肝素剂量的调节 秒 控制倍数 首剂负荷量80IU/kg, 随后18IU/(kg.h)维持 35 90 3.0 停药1h,随后减量 3IU/(kg.h)继续给药低分子量肝素和磺达肝癸钠给药方案药物剂量间隔时间Enoxaparin 1.0 mg/kg 每12 h一次（克赛）or 1.5 mg/kg 每天一次Tinzaparin 175 U/kg 每天一次（亭扎肝素）Fondaparinux 5 mg (体重50 kg)每天一次（磺达肝素）7.5 mg (体重50100 kg)10 mg (体重100 kg)抗凝治疗 肝素需与华法林重叠使用，直到

39、INR达标（2.03.0）2天后再停用肝素。最常用口服药物为华法林，初期应与肝素重叠使用，对于年轻（小于60岁）患者或者既往健康的院外患者而言，起始剂量通常为10mg；而对于老年及住院患者，起始剂量通常为5mg，以后根据国际标准化比值（INR）调整剂量,长期服用者INR宜维持在2.03.0之间。抗凝治疗时程急性肺栓塞的抗凝时间长短应个体化，一般至少需要3个月。如果急性肺栓塞（0.55患者）发展成慢性血栓栓塞性肺动脉高压者应长期抗凝治疗。如果急性肺栓塞治疗成功，症状基本消失，无右心压力负荷，影像学检查肺栓塞基本消失者应根据血栓形成的诱发因素类型决定抗凝时程。抗凝治疗时程由暂时或可逆性诱发因素（服

40、用雌激素、临时制动、创伤和手术）导致的肺栓塞患者推荐抗凝时程为3个月。对于无明显诱发因素的首次肺栓塞患者（特发性静脉血栓）建议抗凝至少3个月，3个月后评估出血和获益风险再决定是否长期抗凝治疗，对于无出血风险且方便进行抗凝监测的患者建议长期抗凝治疗。对于再次发生的无诱发因素的肺栓塞患者建议长期抗凝。对于静脉血栓栓塞危险因素长期存在的患者应长期抗凝治疗，如癌症患者、抗心脂抗体综合征、易栓症等。可疑患者体征、心电图、超声心动图、D-二聚体、血气分析、心肌酶 高度可疑即可抗凝治疗 肺动脉增强CT或核素肺灌注危险分层（血压、右心负荷、心肌酶）高危中危低危 溶栓 抗凝 院外抗凝急性肺栓塞诊治流程下腔静脉滤

41、器植入适应证肺栓塞合并抗凝治疗禁忌或抗凝治疗出现并发症者充分抗凝治疗后肺栓塞复发者高危患者的预防：广泛、进行性静脉血栓形成；行导管介入治疗或肺动脉血栓剥脱术者；严重肺动脉高压或肺心病者。 因滤器只能预防肺栓塞复发，并不能治疗DVT，因此安装滤器后如无抗凝禁忌仍需抗凝，防止进一步血栓形成。预防机械性措施可计量压力的弹力袜（ES）间断充分压迫装置（ IPC）可促使血管内皮纤维蛋白溶解，因此可用于高出血风险患者或作为在药物抗凝基础上的辅助预防措施。小剂量肝素（ LDUH）联合ES、IPC组更有效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. 药物预防（1）预防应以抗凝血酶药物为主，不主张单独阿司匹林预防。LMWH的安全性好，其预防效果与UFH5000IU，2次/d相似。对有危险因素的小手术、年龄40-60岁或有危险因素的非大型手术的中度危险患者，推荐使用UFH5000IU，2次/d或LMWH3400IU/d。对年龄大于60岁或有危险因素的非大型手术患者，年龄大于40岁或有危险因素需大型手术的高危患者，推荐使用UFH5 000IU，3

43、次/d或LMWH3 400IU/d。药物预防（2）对有多种危险因素的极高危患者，推荐选用戊聚糖钠、LMWH或维生素K拮抗剂，预防用药至少10d。大多数ICU患者都需要使用LDUH或LMWH进行预防性抗凝。ACCP-7首次公布对长途旅行者静脉血栓栓塞症预防的建议：如果飞行时间超过6h，无论有无PTE-DVT危险因素，旅行者都应该进行腓肠肌仲缩、避免穿使下肢和腰部紧身的衣裤、避免脱水，对有PTE-DVT危险因素者应考虑使用ES或旅行前皮下注射一剂LMWH。静脉血栓栓塞的预防不再推荐的抗凝药物包括：达那肝素（danaparoid）、重组水蛭素和低分子右旋糖酐等，也不主张采用调整剂量的UFH进行预防性

44、抗凝治疗。静脉血栓栓塞症VTE = Deep Vein Thrombosis (DVT) +Pulmonary Embolism (PE)Thrombus in oneof the deep veinsEmbolusPerfusion defectVTE是沉寂的“杀手”!第3位最常见的血管疾病Symptomatic VTE AsymptomaticVTE/site/Alaska.phpOver 70% PEare detected“POSMORTEM”Between 50%- 80% of DVTs are clinically silent(Stein,1995), (Lethen, 1997)深静脉血栓临床症状 DVT可以无症状，