1、,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,深静脉血栓形成（deep v
2、enous 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VTE,PTE: 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 physical s
3、igns,96% 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 thrombophlebi
4、tis 24% have lower extremity edema 23% have a cardiac murmur 19% have cyanosis,Original Geneva Score,Age:60 79 years (1 point) 80+ years (2 points) Previous DVT or PE (2 points) Recent surgery within 4 weeks (3 points) Heart rate 100 beats per minute (1 point) PaCO2 (partial pressure of CO2 in arter
5、ial blood):35mmHg (2 points) 35 - 39mmHg (1 point) PaO2 (partial pressure of O2 in arterial blood):49mmHg (4 points) 49 - 59mmHg (3 points) 60 - 71mmHg (2 points) 72 - 82mmHg (1 point),Revised Geneva Score,Age 65 years or over (1 point) Previous DVT or PE (3 points) Surgery or fracture within 1 mont
6、h (2 points) Active malignant condition (2 points) Unilateral lower limb pain (3 points) Haemoptysis (2 points) 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 interpret
7、ation,The score obtained relates to probability of PE: 0 - 3 points indicates low probability (8%) 4 - 10 points 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 n
8、ature of, further investigations such as D-dimer, ventilation/perfusion scanning and CT pulmonary angiography to confirm or refute the diagnosis of PE.,Geneva Scoring for Pulmonary Embolism Simplified Further,1 age over 65 2 history of deep venous thrombosis or pulmonary embolism 3 surgery under gen
9、eral anesthesia or lower-limb fracture within 1 month 4 active malignancy 5 unilateral lower-limb pain 6 hemoptysis 7 heart rate between 75 and 94, or 95 and above 8 pain on lower-limb palpation and unilateral edemaPatients with scores of 2 or less were considered unlikely to have pulmonary embolism
10、 under the revised scoring. Although no patients in the “unlikely“ group with normal D-dimer levels developed pulmonary embolism during 3 months follow-up, the authors estimate that in clinical practice, the probability of pulmonary embolism would be up to 3% in this patient population.,Simplified G
11、eneva Score,Age 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 (1 point) Hemoptysis (1 points) Pain on deep palpat
12、ion 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 patients having a PE with a simplified Geneva score less
13、 than 2 and a normal D-Dimer is 3 percent.,The Wells score,clinically 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 DVT or PE - 1.5 points hemoptysis - 1.0 points mal
14、ignancy (treatment for within 6 months, palliative) - 1.0 points Traditional interpretation Score 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 diagnostic imaging. Score 4 or less - PE unlikely. Cons
15、ider D-dimer to rule out PE.,Wells Score for DVT,Variable 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 point Localized tenderness along the distribution
16、 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 pointAlternative diagnosis as likely or more possible than t
17、hat of DVT -2 points,Modified Wells Score (Canadian score) for clinical probablity of PE is:,Variable Score Clinical signs of DVT +3 points Alternative diagnosis less probable than PE +3 points Heart rate 100 bpm +1.5 pointsImmobilization or surgery 6 indicates a high probability of PE.,肺栓塞,静脉血栓栓塞症
18、Venous thromboembolism: DVT & PE,深静脉血栓DVT,肺栓塞PTE,https:/ that originated in the femoral vein of the leg, removed from a pulmonary artery,Large thrombus in the femoral vein of the leg,PE的常见症状,呼吸困难 最常见，约占84%90%。 胸痛 约占70% 咯血 约占30% 惊恐 约占55% 咳嗽 约占37% 晕厥 约占13%,体格检查,一般检查 低热，约占43% 呼吸频率增快，约占70% 窦速，约占44% 紫绀，约
19、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,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 EMBOLISM DIAGNOSIS,EKG The classic findings of righ
20、t 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 fibrillation Only 20% of patients with proven PE have any of these classic ECG abnormalities,心电图EKG,V1-V4的T波改变和ST段异常； 部分病人出现SIQIIIT
21、III； 不完全的右束支传导阻滞、 肺性P波、 电轴右偏和顺钟向转位。 常见窦速。,PULMONARY EMBOLISM DIAGNOSIS,EKG 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。,超声心动检查,间接征象：右室扩张为71%100%，右肺动脉内径增加72%，左室径变小38%，室间隔左移及矛盾运动42%以及肺动脉压增高等。 直接征象：右心血栓可有两个类型：活动、蛇样运动的组织和不活动、无蒂及致密的组织。发生PE前者98% ，后者40%。 超声心动图检查对可疑非
22、高危PE的诊断意义不大，敏感性有限（60%70%，特异性90%左右），而且阴性结果也不能排除PE。对于这部分非高危PE患者，超声的主要作用是预后分层，中危，抑或低危。 当临床评估结果与无创影像检查结果不一致时，可考虑肺动脉造影检查。,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 Ultrasonography,Relies on loss of vein compressibility as the primary criterion About 1/3 of pts will have no imaging eviden
23、ce of DVT Clot may have already embolized Clot 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
24、清晰地探测位于主、叶及段肺动脉内的栓子。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。,CXR,Initial CXR usually normal. May progress to
25、 show atelectasis, plueral effusion and elevated hemidiaphram. Hamptons hump and Westermark sign are classic findings but are not usually present.,PULMONARY EMBOLISM DIAGNOSIS,Chest X-ray: virtually always normal may show Westermarks sign, a dilatation of the pulmonary vessels proximal to an embolis
26、m, sometimes with a sharp cutoff rare late finding is Hamptons hump, a triangular or rounded pleural-based infiltrate with the apex pointed toward the hilum, frequently located adjacent to the diaphragm,Chest X-ray findings:,Band atelectasis (1 point) Elevation of hemidiaphragm (1 point) The score o
27、btained relates to the probability 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 visc
28、eral pleural surface and a rounded convex apex directed toward the hilum; associated with pulmonary infarct,Westermark 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 c
29、lot or by reflex vasoconstriction,Radiographic Eponyms - Hamptons Hump, Westermarks Sign,Westermarks Sign,Hamptons Hump,CXR,Hamptons Hump consists of a pleura based shallow wedge-shaped consolidation in the lung periphery with the base against the pleural surface.,PULMONARY EMBOLISM DIAGNOSIS,Wester
30、marks Sign,PULMONARY EMBOLISM DIAGNOSIS,Hamptons Hump,PE with hemorrhage or pulmonary edema,PE with effusion and elevated diaphragm,V/Q Scan,Ventilation-perfusion scanning is a radiological procedure which is often used to confirm or exclude the diagnosis of pulmonary embolism. It may also be used t
31、o monitor treatment. Ventilation (V) Achieved by 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 aggre
32、gated albumin (MAA). An embolus shows up as a cold area when the patient is placed under a gamma camera.,Abnormal V/Q Scan,Abnormal V/Q Scan,Perfusion,Ventilation,V/Q Scan Results,Likelihood of pulmonary embolism according to scan category and clinical probability in PIOPED study,Spiral CT,Spiral CT
33、 first introduced in 1990s In 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 helical CT the X-ray source and detectors are attached to a fre
34、ely 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 CT,Major advantage of Spiral CT is speed: Often the patient can hold their breath for the entire study, reducing motion
35、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 disease. Sensitive for PE in the proximal pulmonary arte
36、ries, but less so in the distal segments.,CT Angiogram,Quickly 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 can be used to follow up “non diagnostic V/Q scans
37、.,CT Angiogram,Chest computed tomography scanning demonstrating extensive embolization of the pulmonary arteries.,Diagnosis Spiral CT/ Multislice,Ascending Aorta,Lt Pulmonary Artery,Main Pulmonary Artery,Rt Pulmonary Artery,Descending Aorta,Thrombus,Pulmonary embolism,This 62 y/o female presented wi
38、th 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，
39、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 bothmain pulmonary arteries.,CT pulmonary angiography (CTPA) showing a saddle embolus and substantial thrombus burden in the loba
40、r branches of both main pulmonary arteries.,Asian/Pacific Islanders (12.1M),450 - 600,000 episodes/year in US,Stein et al: Regional Differences in Rates of Diagnosis and Mortality of Pulmonary Thromboembolism; AJC 2004;93:1194-1197,2008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。
41、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 溶栓或栓子切除术 (15%)中危
42、+ + (3-15) + 住院治疗 +低危(1%) 早期出院或院外治疗,非高危,a:当出现低血压后休克时就不需要评估右心功能和心肌损伤情况。,可疑高危肺栓塞的诊断流程图,图1 可疑高危肺栓塞的诊断流程图,可疑高危PE的诊断策略,高危PE患者存在低血压或休克，随时有生命危险，需要尽快做出诊断，并与心源性休克、急性瓣膜功能障碍、心包填塞和主动脉夹层进行鉴别，此时超声心动图是首要的检查方法。对于PE患者，超声心电图常常可以显示肺动脉高压和右室负荷过重的间接征象，有时经胸超声可以直接显示位于右心、主肺动脉或左、右肺动脉内的血栓。有条件的中心可以选择经食道超声。对于高度不稳定的患者，或不能进行其他检查，
43、可根据超声结果做出PE诊断（图1）。若支持治疗后，患者病情稳定，应行相应检查以明确诊断，CT肺血管造影常常可以确诊。由于病情不稳定的患者经导管进行肺动脉造影死亡风险高，且增加溶栓的出血几率，指南不建议应用。,可疑非高危急性肺栓塞诊断流程,可疑非高危PE的诊断策略,CT肺动脉造影已成为确诊可疑PE的主要胸部影像学检查。肺通气/灌注显像由于结果的非确定性比例较高，应用已减少，但仍不失一有效的选择。由于绝大多数的可疑非高危PE并不是真正的PE，因此指南不建议将CT作为这类患者的一线检查（图2）。有研究显示，急诊收治的可疑PE患者，经过合理的血浆D二聚体测定，结合临床可能性，可以排除大约30%的PE，
44、这部分患者不予抗凝治疗，随访3个月，结果发生血栓栓塞的风险不足1%。对于临床高可能性的患者，单为诊断而言，不推荐测定D-二聚体，因为即便应用高敏感度的分析方法所得到的正常D-二聚体值也不能排除PE。,2008年溶栓建议,心源性休克及/或持续低血压的高危肺栓塞患者，如无绝对禁忌证，溶栓治疗是一线治疗。 高危患者存在溶栓禁忌时可采用导管碎栓或外科取栓。 导管内溶栓与外周静脉溶栓效果相同。 对非高危(中危、低危）患者不推荐常规溶栓治疗。 对于一些中危患者全面权衡出血获益风险后可给予溶栓治疗。 低危患者不推荐溶栓治疗。,溶栓治疗时间窗,溶栓时间窗通常在急性肺栓塞发病或复发后2周以内，症状出现48小时内
45、溶栓获益最大，溶栓治疗开始越早，疗效越好。,溶栓药物及溶栓方案,链激酶：25万IU静脉负荷，给药时间30分钟，继以10万IU/h维持12-24小时 快速给药：150万IU静点2小时 尿激酶：4400IU/Kg静脉负荷量10min，继以4400IU/Kg/h维持12-24小时快速给药：300万IU静点2小时 rt-PA ： 100mg静点2小时 或0.6mg/Kg静点15分钟（最大剂量50mg）,急性肺栓塞溶栓治疗禁忌证,绝对禁忌证任何时间出血性或不明原因的脑卒中6个月内缺血性脑卒中中枢神经系统损伤或肿瘤3周内大创伤、外科手术、头部损伤近一月内胃肠道出血已知的活动性出血,相对禁忌证6个月内短暂性
46、脑缺血发作口服抗凝药妊娠或分娩1周内 不能压迫的血管穿刺创伤性心肺复苏难治性高血压(收缩压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
47、用指征 血流动力学不稳定的高危肺栓塞患者（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
48、（通常是1.5倍2.0倍）。,根据体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),
