pulmonary embolism: diagnostic algorithms - registro ep polmonare/01_favretto...  pulmonary...

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Introduction

In 2005, the diagnosis of acute pul-monary embolism (PE) still remains a com-mon, major, vexing and elusive clinicalproblem. The ideal diagnostic test shouldbe accurate, safe, readily available, easy tointerpret and cost-effective. Unfortunately,none of the available tests meets all thesecriteria. This holds true for pulmonary an-giography as well, that has been generallyconsidered the gold standard in the diag-nostic work-up of PE.

Clinical suspicion of pulmonaryembolism

In 90% of cases the clinical suspicionof PE is raised by clinical signs and symp-toms, especially if patients present withclinical evidence of deep venous thrombo-sis or at risk for venous thromboembolism.Only in 10% of cases, PE is suspected be-cause of incidental electrocardiographic orarterial blood gas analysis or radiologicalfindings (chest X-ray or helical computedtomography).

Approximately 25-30% of patients withclinically suspected PE really have PE1.

In the context of a recent trial2 whichenrolled 756 consecutive patients with clin-ically suspected PE collected from theemergency departments of three teachinghospitals, the prevalence of PE was 26%.

The clinical signs and symptoms aloneof PE are non-specific; as a consequencethe clinical diagnosis of PE is very often in-accurate. In order to improve clinical accu-racy, it is therefore necessary to use addi-tional tests which include imaging tech-niques.

First-level tests (first-line diagnostictests), available in all hospitals, readily andeasily performed, are the following: elec-trocardiography, arterial blood gas analysis,and chest X-ray. Unfortunately the diagnos-tic value of each test is poor (Table I)3,4.

Clinical probability or pre-testprobability

The combination of all these variables(risk factors for venous thromboem-bolism or documented deep venousthrombosis, signs or symptoms sugges-tive of PE, results of first-level tests) al-lows a fairly accurate stratification of pa-tients with clinical suspicion of PE in

Key words:Diagnostic algorithms;Diagnostic strategy;Pulmonary embolism.

2005 CEPI Srl

Address:

Dr. Giuseppe Favretto

U.O. di CardiologiaRiabilitativa e PreventivaOspedale Riabilitativodi Alta SpecializzazioneVia Padre Bello, 331045 Motta di Livenza (TV)E-mail:giuseppe.favretto1@tin.it

Pulmonary embolism: diagnostic algorithmsGiuseppe Favretto, Paolo Stritoni*

Division of Cardiac Rehabilitation, Rehabilitation Hospital, Motta di Livenza (TV), *Division of Cardiology,General Hospital, Treviso, Italy

In 90% of cases the clinical suspicion of pulmonary embolism (PE) is raised by clinical signs andsymptoms, while in only 10% of cases PE is suspected on the basis of electrocardiographic, arterialblood gas analysis or radiological findings.

The combination of clinical signs and symptoms and the results of first-level diagnostic tests (elec-trocardiography, gas analysis and chest X-ray) allows a fairly accurate classification of patients withclinical suspicion of PE into three categories of clinical (or pre-test) probability: low, intermediateand high.

The clinical diagnosis of PE is very often inaccurate making the use of additional tests, includingimaging techniques, mandatory.

The choice and the combination (= diagnostic algorithms) of second- and third-level diagnostictests (D-dimer, venous ultrasound, echocardiography, lung scintigraphy, helical computed tomogra-phy and pulmonary angiography) depend primarily on the clinical conditions of patients and theirpre-test probability.

We propose two diagnostic algorithms: 1) a diagnostic algorithm for patients with clinically sus-pected PE and critical clinical conditions (unstable patients), 2) a diagnostic algorithm for patientswith clinically suspected PE and non-critical clinical conditions (hemodynamically stable patients).

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three categories of clinical or pre-test probability:low, intermediate and high clinical probability or pre-test probability of PE.

Clinical probability may be estimated empiricallyor by a prediction score. The main advantage of a pre-diction score is to allow a standardized evaluation. Themost prospectively valid scores are the simple clinicalmodels devised by Wells et al.5 and the score of theGeneva Group6; the score system, of the PISAPEDstudy4 has not been validated externally. A recent studywhich compared the performance of these three modelsin 215 consecutive patients with PE showed a very im-portant difference in defining precisely the pre-testprobability of PE7.

It has not been demonstrated yet that grading clini-cal probability by scoring systems represents a moreaccurate method than the empirical assessment under-taken by an experienced physician8.

In all patients with possible PE, clinical probabilityshould be assessed and documented9. However, thepositive predictive value of high clinical probability isapproximately 70-75% whereas the negative predictivevalue of low clinical probability is approximately 85-90%. Therefore, it is necessary to use second- andthird-level diagnostic tests.

Second-level diagnostic tests, available in all hospi-tals, are the following: laboratory assays (D-dimer, tro-ponin, brain natriuretic peptide), venous ultrasound,and echocardiography.

Third-level imaging tests, not available in all hos-pitals, are the following: lung scintigraphy, helical(spiral) computed tomography, magnetic resonanceangiography, and pulmonary angiography.

Diagnostic strategy

The choice and the combination of diagnostic tests(diagnostic algorithms, diagnostic work-up) dependson:

1) clinical conditions of patients with clinically sus-pected PE (critical or non-critical, presence or absenceof prior cardiopulmonary disease);2) clinical or pre-test probability (low, intermediate orhigh; rule out/rule in strategy);3) suspected PE in outpatients or in hospitalized pa-tients;4) predictive accuracy of diagnostic tests as obtained byclinical evaluation (virtual accuracy);5) local availability of diagnostic tests;6) local predictive accuracy of diagnostic tests (realaccuracy) as obtained by experienced professionalsand equipments;7) cost-effectiveness analysis of diagnostic strategiesand risk-benefit ratio.

Diagnostic algorithms

Diagnostic algorithm for patients with clinicallysuspected pulmonary embolism and critical clinicalconditions (unstable patients) (Fig. 1). The definitionof critical clinical conditions is as follows10: patients with hemodynamic instability (cardiac arrest,shock, hypotension); patients without hemodynamic instability but with atleast one of the following: a) important, persistent andworsening dyspnea; and b) recent syncope.

No absolute as well as validated algorithm is avail-able for unstable patients with clinically suspected PE;diagnosis is influenced by the necessity to take urgenttherapeutic measures.

Diagnostic algorithm for patients with clinicallysuspected pulmonary embolism and non-criticalclinical conditions (hemodynamically stable pa-tients) (Figs. 2 and 3). The diagnostic strategy and al-gorithm mainly depend on the pre-test probability: A) patients with clinically suspected PE and high pre-test probability of PE (approximately 20% of all pa-

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Table I. Diagnosis of pulmonary embolism (PE): first-level tests.

Sensitivity Specificity

ECGVersus PE 70% Intermediate/highVersus massive PE 95% Intermediate/low

Arterial blood gas analysisVersus PE 85% Low in COPD and elderly patients

High in healthy and young subjectsVersus massive PE 95% Low

Chest X-rayPatients without prior cardiopulmonary disease High LowPatients with prior cardiopulmonary disease Low Very lowPIOPED3 88% LowPISAPED4 86% High

COPD = chronic obstructive pulmonary disease.

tients with clinically suspected PE) have documentedPE in 70% of cases (positive predictive value of highpre-test probability: 70%).

For those patients with high pre-test probability thefollowing diagnostic tests are advised: lung scintigra-

phy, helical computed tomography, and echocardiogra-phy.

Patients with high pre-test probability, if necessary,may undergo pulmonary angiography for diagnosis ofPE11.

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Figure 1. Proposed diagnostic algorithm for suspected pulmonary embolism (PE) in the presence of critical clinical conditions. CT = computed to-mography.

Figure 2. Proposed diagnostic algorithm for suspected pulmonary embolism (PE) in clinically stable patients in hospitals with all diagnostic tests avail-able. CT = computed tomography; LS = lung scan; PA = pulmonary angiography; US = ultrasound.

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Figure 3. Proposed diagnostic algorithm for suspected pulmonary embolism (PE) in clinically stable patients in hospitals without Nuclear Medicine.CT = computed tomography; PA = pulmonary angiography; US = ultrasound.

Figure 4. Proposed diagnostic algorithm for suspected pulmonary embolism (PE) in clinically stable Emergency Room patients with non-high pre-testprobability. AC = anticoagulants; BNP = brain natriuretic peptide; CT = computed tomography; ECG = electrocardiography; F = fibrinolytics; US =ultrasound.

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Figure 5. Proposed diagnostic algorithm for suspected pulmonary embolism (PE) in clinically stable hospitalized patients with non-high pre-test probabil-ity. AC = anticoagulants; BNP = brain natriuretic peptide; CT = computed tomography; ECG = electrocardiography; F = fibrinolytics; US = ultrasound.