Is Outpatient Treatment Finally an Option for Pulmonary Embolism?

Is this treatment modality finally a viable option?

Your next patient is a 33-year-old female with chief complaint of dyspnea with exertion. She is mildly tachycardic at 102, but the rest of her vital signs are normal. She expresses that she returned from an overseas trip over one week ago, and since that time she has noticed she cannot climb stairs without becoming short of breath. She has also noted chest pain that is sharp in nature. She has no medical problems and no allergies, takes no medications except for Tylenol as needed, and has no prior surgeries. Your physical exam, including extremities, lungs, and heart, is normal. Her pregnancy test is negative. Your clinical gestalt screams pulmonary embolism. Her ECG is normal, except for tachycardia, and her O2 saturation is 98% at rest. Her chest X-ray, troponin, pro-BNP, venous lactate, and other laboratory studies are normal. Her CT with contrast shows left sided segmental pulmonary embolism (PE). You’ve always admitted these patients, but you’ve heard some of your colleagues have been discharging patients with PE. Is this safe? Can you do this?

Background
Classically patients have been admitted for PE. The early 2000s saw the beginning of outpatient treatment, primarily in Canada, where close to 50% of PE patients were safely treated as outpatients [^2,3]. This is not the same in the U.S., where over 98% of patients with PE were admitted in 2015 [4].  Recent studies suggest outpatient therapy is safe and effective for patients, as long as they can be risk stratified as low risk for major adverse event (such as death) [^1,5-8]. The American College of Chest Physicians (ACCP) 2016 guidelines give a grade 2B recommendation for outpatient therapy for PE in low-risk settings with adequate home circumstances and follow up, and no other indications for hospital admission [1]. 

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This sounds too good to be true, but wait…we’re getting ahead of ourselves. This article will not evaluate ED testing or imaging for PE but rather outpatient therapy. So with this background, let’s get to it.

Before we even talk about ambulatory risk stratification, let’s review major exclusions to ambulatory treatment: hemodynamic instability (hypotension, altered mental status), severe pain, hypoxemia, signs of right ventricular strain (increase in serum biomarkers (troponin or BNP) or RV strain on ultrasound (US) or CT scan), medical comorbidities that otherwise need admission, and elevated risk of bleeding [^1,5-8].

Per ACCP guidelines, patients with low-risk PE and adequate social situation may be treated at home (Grade 2B recommendation). Also per guidelines, subsegmental PE with no involvement of the proximal pulmonary arteries and no proximal DVT who are low risk for recurrent VTE may receive clinical surveillance over anticoagulation (Grade 2C recommendation), though if high risk for recurrent VTE, anticoagulation may be warranted (Grade 2C recommendation) [1]. An agreement with another service, such as internal medicine or primary care, should be obtained to ensure patient follow up.

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Risk Stratification
A number of tools for risk stratification do exist, including the PE severity index (PESI) [^8-12], simplified PESI (sPESI) [^13-15], Geneva Prognostic Score [^16-20], Global Registry of Acute Coronary Events (GRACE) [^21], Hestia exclusion criteria [^7,2], European Society of Cardiology [^6], and the Aujesky score [^23,24]. There is no consensus on which clinical score or criteria to use, and not all demonstrate sufficient sensitivity for clinical reassurance [^1,8]. A review of clinical prediction rules with the highest sensitivities (ranging from 80% to over 90%) classified 22-45% of patients as low risk for mortality in the respective study populations [^8].

PESI was designed to estimate mortality at 30 days based on 11 factors (Table 1) [^8-12]. This score demonstrates a sensitivity of 89% and specificity of 49% for predicting 30 day mortality.8 Simplified PESI  (sPESI) uses 7 factors (Table 1 below), and 1 point on this scale places the patient in the moderate to higher risk category, excluding outpatient management [^8,13-15]. Sensitivity of sPESI for 30 day mortality is 92-96.1%, with specificity 38% [^8,13-15]. Both PESI and sPESI perform similarly in identification of low risk patients, though a recent report suggests that sPESI may over-classify patients as higher-risk [^25]. However, over-classification would be safer from the EM perspective [^25]. The PESI and sPESI appear to be the most popular in the U.S. at this time, and we authors use the PESI/sPESI scores.

The Hestia Criteria ask more questions about the safety of discharging a PE patient – including bleed risk, renal insufficiency, liver impairment, pregnancy, or medical or social reasons for admissions (Table 2 below). If any one of the 11 Hestia criteria is met, the patient is too high-risk to be treated at home. Sensitivity of Hestia approaches 82% with specificity 56% for identifying low risk patients [^7,8,22]. When PE patients in the Netherlands who had been triaged to inpatient or home using Hestia were scored, post-hoc, by sPESI, researchers found similar sensitivity and NPV for 30-day mortality in both scores [^22].

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Hestia Criteria were not included in a recent meta-analysis due to inadequate data [^8], but we expect more studies to evaluate its mortality predictions in the coming years. Other tools include GRACE, Aujesky score, and RIETE score, but these tools suffer from difficulty of use in the ED, poor performance, or low supporting evidence [^{21,23,24,26].}

Use of Ultrasound in PE
Ultrasound can play a role in risk-stratification for PE, but typically is helpful accelerating the diagnosis in undifferentiated unstable patients, before CT. Ultrasound views primarily will evaluate for signs of RV strain using parasternal (long and short axis), subcostal, and apical views. RV dysfunction is a criterion for submassive PE [^27-31]. A recent study in 2013 conducted by emergency physicians at the bedside suggested RV dilatation possesses a 98% specificity and 50% sensitivity for diagnosis of PE [^27]. However, most PE’s will demonstrate no acute findings on US [^27-31].

The European Society of Cardiology (ESC) low-risk PE criteria incorporate US and biomarkers.6 Risk scores without biomarkers and US may be used alone to risk stratify patients, but the latter both offer the ability to evaluate for RV strain, which, if found, would preclude outpatient management [^32-38].

Ambulatory Treatment and Health Care Pressures
The literature consistently demonstrates outpatient therapy is safe and efficacious, as long as the patient is appropriately stratified as low-risk for an adverse event [^{3,7,15,22,32-35].}

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In 2017, healthcare systems are under increasing pressure to move care to an ambulatory setting, but we are not at the point that any PE risk-stratification tool can be chosen and followed without exercising clinical judgment. It’s helpful to consider variables beyond any one scoring system before determining that a specific patient is appropriate for outpatient management. However, there is now literature that outpatient therapy for PE is safe and feasible, as long as the patient is appropriately stratified as low risk [^1,5,7,8]. Ambulatory and admitted patients demonstrate similar proportions of adverse events and bleeding (both approaching less than 1%) [^{3,7,15,22,32-35].}

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The patient in our opening case has a sPESI of 0, she appears well, and her troponin is negative. Her CT scan shows a left segmental PE, with no evidence of heart strain. Her bedside ultrasound appears normal, and it appears she is at low risk for adverse event. You discuss the diagnosis and potential options with the patient, and she wants to go home. What treatment options do you have? The next installment of this series will evaluate anticoagulation regimens, as well as provide a summary for a potential treatment pathway.

*Note: For a more in-depth discussion of the controversies associated with outpatient PE therapy, risk scores, NOACs, and an algorithm, please see the Journal of Emergency Medicine’s article-in-press: Long B, Koyfman A. Best Clinical Practice: Controversies in Outpatient Management of Acute Pulmonary Embolism. JEM 2017; article in press. DOI: http://dx.doi.org/10.1016/j.jemermed.2016.11.020

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