2014ESC急性肺栓塞诊断和管理指南(英文版)(4)

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The detrimental effects of acute PE on the RV myocardium and the

circulation are summarized in Figure1.

Respiratory failure in PE is predominantly a consequence of haemodynamic disturbances.79Low cardiac output results in desat-uration of the mixed venous blood.In addition,zones of reduced ?ow in obstructed vessels,combined with zones of over?ow 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 foramen ovale can be detected by echocardiography:this is caused by an inverted pressure gradient between the right atrium and left atrium and may lead to severe hypoxaemia and an increased risk of paradoxical embolization and stroke.80Finally,even if they do not affect haemodynamics,small distal emboli may create areas of alveo-lar haemorrhage resulting in haemoptysis,pleuritis,and pleural effu-sion,which is usually mild.This clinical presentation is known as ‘pulmonary infarction’.Its effect on gas exchange is normally mild, except in patients with pre-existing cardiorespiratory disease. 2.5Clinical classi?cation of pulmonary embolism severity

The clinical classi?cation of the severity of an episode of acute PE is based on the estimated PE-related early mortality risk de?ned by in-hospital or30-day mortality(Figure2).This strati?cation,which has important implications both for the diagnostic and therapeutic strategies proposed in these guidelines,is based on the patient’s clin-ical status at presentation,with high-risk PE being suspected or con-?rmed in the presence of shock or persistent arterial hypotension and not high-risk PE in their absence.3.Diagnosis

Throughout these Guidelines and for the purpose of clinical manage-ment,‘con?rmed PE’is de?ned as a probability of PE high enough to indicate the need for PE-speci?c treatment,and‘excluded PE’as a probability of PE low enough to justify withholding PE-speci?c treat-

ment with an acceptably low risk.

3.1Clinical presentation

PE may escape prompt diagnosis since the clinical signs and symptoms

are non-speci?c(Table3).When the clinical presentation raises the suspicion of PE in an inpidual patient,it should prompt further objective testing.In most patients,PE is suspected on the basis of dys-pnoea,chest pain,pre-syncope or syncope,and/or haemoptysis.81–83 Arterial hypotension and shock are rare but important clinical pre-sentations,since they indicate central PE and/or a severely reduced haemodynamic reserve.Syncope is infrequent,but may occur regard-

less of the presence of haemodynamic instability.84Finally,PE may

be completely asymptomatic and be discovered incidentally during diagnostic work-up for another disease or at autopsy.

Chest pain is a frequent symptom of PE and is usually caused by

pleural irritation due to distal emboli causing pulmonary infarction.85

In central PE,chest pain may have a typical angina character,possibly

re?ecting RV ischaemia and requiring differential diagnosis with acute coronary syndrome(ACS)or aortic dissection.Dyspnoea may be

acute and severe in central PE;in small peripheral PE,it is often

mild and may be transient.In patients with pre-existing heart failure

or pulmonary disease,worsening dyspnoea may be the only symptom indicative of PE.

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is also often present.The chest X-ray is frequently abnormal and,al-though its?ndings are usually non-speci?c in PE,it is useful for exclud-ing other causes of dyspnoea or chest pain.89Electrocardiographic changes indicative of RV strain,such as inversion of T waves in leads V1–V4,a QR pattern in V1,S1Q3T3pattern,and incomplete or complete right bundle-branch block,may be helpful.These elec-trocardiographic changes are usually found in more severe cases of PE;90in milder cases,the only anomaly may be sinus tachycardia, present in40%of patients.Finally,atrial arrhythmias,most frequently atrial?brillation,may be associated with acute PE.

3.2Assessment of clinical probability Despite the limited sensitivity and speci?city of inpidual symptoms, signs,and common tests,the combination of?ndings evaluated by clinical judgement or by the use of prediction rules allows to classify patients with suspected PE into distinct categories of clinical or pre-test probability that correspond to an increasing actual preva-lence of con?rmed PE.As the post-test(e.g.after computed tomog-raphy)probability of PE depends not onlyon the characteristics of the diagnostic test itself but also on pre-test probability,this has become a key step in all diagnostic algorithms for PE.

The value of clinical judgement has been con?rmed in several large series,91–93including the Prospective Investigation On Pulmonary Embolism Diagnosis(PIOPED).94Note that clinical judgement usually includes commonplace tests such as chest X-ray and electro-cardiogram for differential diagnosis.However,clinical judgement lacks standardization;therefore,several explicit clinical prediction rules have been developed.Of these,the most frequently used

A number of D-dimer assays are available.110,111The quantitative enzyme-linked immunosorbent assay(ELISA)or ELISA-derived

assays have a diagnostic sensitivity of95%or better and can therefore

be used to exclude PE in patients with either a low or a moderate

pre-test probability.In the emergency department,a negative ELISA

D-dimer,in combination with clinical probability,can exclude the

disease without further testing in approximately30%of patients

with suspected PE.100,112,113Outcome studies have shown that the

three-month thromboembolic risk was,1%in patients left untreated

on the basis of a negative test result(Table5);99,112–116these?ndings

were con?rmed by a meta-analysis.117

Quantitative 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 PE-unlikely patients as well as in patients

with a low clinical probability.99,100,105Their safety in ruling out PE

has not been established in the intermediate clinical probability cat-

egory.Point-of-care tests have moderate sensitivity,and data from outcome studies in PE are lacking,with the exception of a recent

primary care-based study using the Simplify D-dimer assay,118in

which the three-month thromboembolic risk was1.5%in PE-unlikely patients with a negative D-dimer.

The speci?city of D-dimer in suspected PE decreases steadily with

age,to almost10%in patients.80years.119Recent evidence sug-

gests using age-adjusted cut-offs to improve the performance of

D-dimer testing in the elderly.120,121In a recent meta-analysis,

age-adjusted cut-off values(age x10m g/L above50years)allowed increasing speci?city from34–46%while retaining a sensitivity

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above97%.122A multicentre,prospective management study evalu-ated this age-adjusted cut-off in a cohort of3346patients.Patients with a normal age-adjusted D-dimer value did not undergo computed tomographic pulmonary angiography and were left untreated and formally followed up for a three-month period.Among the766 patients who were75years or older,673had a non-high clinical prob-ability.On the basis of D-dimer,using the age-adjusted cut-off (instead of the‘standard’500m g/L cut-off)increased the number of patients in whom PE could be excluded from43(6.4%;95%CI 4.8–8.5%)to200(29.7%;95%CI26.4–33.3%),without any addition-al false-negative?ndings.123D-dimer is also more frequently elevated in patients with cancer,124,125in hospitalized patients,105,126and during pregnancy.127,128Thus,the number of patients in whom D-dimer must be measured to exclude one PE(number needed to

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test)varies between3in the emergency department and≥10in the speci?c situations listed above.The negative predictive value of a (negative)D-dimer test remains high in these situations.

3.4Computed tomographic pulmonary angiography

Since the introduction of multi-detector computed tomographic (MDCT)angiography with high spatial and temporal resolution and quality of arterial opaci?cation,computed tomographic(CT)angiog-raphy has become the method of choice for imaging the pulmonary vasculature in patients with suspected PE.It allowsadequate visualiza-tion of the pulmonary arteries down to at least the segmental level.131–133The PIOPED II trial observed a sensitivity of83%and a speci?city of96%for(mainly four-detector)MDCT.134PIOPED II also highlighted the in?uence of clinical probability on the predictive value of MDCT.In patients with a low or intermediate clinical prob-ability of PE as assessed by the Wells rule,a negative CT had a high negative predictive value for PE(96%and89%,respectively), whereas this was only60%in those with a high pre-test probability. Conversely,the positive predictive value of a positive CT was high (92–96%)in patients with an intermediate or high clinical probability but much lower(58%)in patients with a low pre-test likelihood of PE. Therefore,clinicians should be particularly cautious in case of discor-dancy between clinical judgement and the MDCT result.

Four studies provided evidence in favour of computed tomog-raphy as a stand-alone imaging test for excluding PE.In a prospective management study covering756consecutive patients referred to the emergency department with a clinical suspicion of PE,all patients with either a high clinical probability or a non-high clinical probability and a positive ELISA D-dimer test underwent both lower limb ultrasonog-raphy and MDCT.113The proportion of patients in whom—despite a negative MDCT—a proximal DVT was found on ultrasound was only 0.9%(95%CI0.3–2.7).113In another study,99all patients classi?ed as PE-likely by the dichotomized Wells rule,or those with a positive D-dimer test,underwent a chest MDCT.The three-month thrombo-embolic risk in the patients left untreated because of a negative CT was low(1.1%;95%CI0.6–1.9).99Two randomized,controlled trials reached similar conclusions.In a Canadian trial comparing V/ Q scan and CT(mostly MDCT),only seven of the531patients (1.3%)with a negative CT had a DVT,and one had a thromboembolic event during follow-up.135Hence,the three-month thromboembolic risk would have been1.5%(95%CI0.8–2.9)if only CT had been used.135A European study compared two diagnostic strategies based on D-dimer and MDCT,one with-and the other without lower limb compression venous ultrasonography(CUS).116In the D-dimer–CT arm,the three-month thromboembolic risk was 0.3%(95%CI0.1–1.2)among the627patients left untreated, based on a negative D-dimer or MDCT.

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