Thursday, November 20, 2014

Severity assessment in pulmonary embolism: a need for consistency

As it does for many conditions, severity assessment of pulmonary embolism guides treatment. Severity assessment for PE is more important than ever these days because treatment options have multiplied. There are now many more decision points than we had just a few years ago. Now under discussion, for example, is the question of which patients can be discharged early or even undergo the entirety of their treatment as outpatients. The approval of target specific oral anticoagulants adds another decision point. Which patients with PE are candidates for those agents? Recent discussions have asked the question of whether there exists a subset of patients with acute PE who don't need to be treated at all. A clinical trial now in progress seeks to address that question. The question regarding how long to anticoagulate patients for secondary prevention is not as open and shut as it was just a few years ago. This is illustrated by a reading of the most recent ACCP guidelines. The same is true regarding indications for IVC filters. Meanwhile the debate about selection of patients for thrombolytic therapy rages on and has recently been complicated by promising studies looking at half dose thrombolytic therapy for a variety of patients with pulmonary embolism.

For us to make sense of all the new evidence and treatment options severity classification becomes important. The problem is this area is evolving too and has become inconsistent across the published literature. I'm going to be blogging about some of the new treatment options in the near future. But in order to have a meaningful discussion it is first important to define the terms of severity classification. What follows is my attempt to review some of the history of PE classification and outline the topic as it stands now, however confusing.

Back in the day it was pretty simple. The binary decision was whether to treat conventionally (with unfractionated or low molecular weight heparin) or to use thrombolytic therapy. It was based on whether the PE was associated with normal blood pressure or hypotension respectively. PE with hypotension correlated with obliteration of 50% or more of the activity on radionuclide perfusion scanning, which was an ancillary criterion. There followed a rising awareness of patients who were normotensive but had a large clot burden and evidence of acute right ventricular dysfunction as measured by biomarkers and/or imaging which consisted usually of echocardiograhy as well, in some centers, as ascertainment of the ratio of right ventricular to left ventricular diameter on CT angiography. With the addition of this intermediate category we then had 3 categories which became known as massive, submassive and hemodynamically normal.

Treatment discussions regarding pulmonary embolism have centered around this classification. For massive PE there has been a fairly strong consensus in favor of thrombolytic therapy in the absence of contraindications. Submassive PEs are the subject of controversy with divided opinion on whether to treat with thrombolysis or conventional heparin therapy with the weight of opinion favoring the latter. Hemodynamically uncomplicated PEs according to the recent thinking are those that could be treated with conventional anticoagulation and considered for early discharge or even outpatient treatment.

With the publication of recent papers suggesting yet another treatment method, half dose thrombolytic in conjunction with anticoagulation, the discussion has been complicated further because these papers have used yet another classification, which stratifies pulmonary emboli into severe, moderate and (by implication) mild forms. The problem is, this new classification does not translate well into the traditional one because it uses criteria (mainly anatomic) that are not analogous. This is illustrated by the MOPETT trial and the more recent drip, dose and discharge (DDD) paper. Here are the definitions form the DDD paper:

Moderate PE was regarded as presence of symptoms plus objective evidence of PE, defined as 70% involvement of a pulmonary artery or 2 lobar or 4 segmental branches plus hemodynamic stability. Severe PE was defined as systolic blood pressure less than of equal to100 mm Hg plus all other features of moderate PE; saddle pulmonary embolism; or involvement of greater than 70% of the main pulmonary artery (PA) with thrombus, irrespective of blood pressure.

MOPETT did not define severe PE because those patients were not studied. The definition of moderate PE was along the same lines as in DDD with a slight variation:

“Moderate” PE was defined as the presence of signs and symptoms of PE plus computed tomographic pulmonary angiographic involvement of greater than 70% involvement of thrombus in greater than or equal to 2 lobar of left or right main pulmonary arteries or by a high probability ventillation/perfusion scan showing ventillation/perfusion mismatch in greater than or equal to two lobes.

In order to have a meaningful discussion of the rapidly emerging literature and treatment options for pulmonary embolism it is important to keep these definitions in mind. In the future we need some sort of a consensus.

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