Is Outpatient Treatment Finally an Option for Pulmonary Embolism?

2 Comments

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]. 

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.

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].

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].

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].

——-

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


REFERENCES

  1. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016;149:315–52.
  2. Kovacs MJ, Anderson D, Morrow B, et al. Outpatient treatment of pulmonary embolism with dalteparin. Thromb Haemost 2000;83:209–11.
  3. Kovacs MJ, Hawel JD, Rekman JF, Lazo-Langner A. Ambulatory management of pulmonary embolism: a pragmatic evaluation. J Thromb Haemost 2010;8:2406–11.
  4. Stein PD, Fatta F, Hughes PG, et al. Home treatment of pulmonary embolism in the era of novel oral anticoagulants. Am J Med 2016; 129:974–7.
  5. Baglin T. Fifty percent of patients with pulmonary embolism can be treated as outpatients. J Thromb Haemost 2010;8:2404–5.
  6. Torbicki A, Perrier A, Konstantinides S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008;29:2276–315.
  7. Beam DM, Kahler ZP, Kline JA. Immediate discharge and home treatment with rivaroxaban of low risk venous thromboembolism diagnosed in two U.S. emergency departments: a one-year preplanned analysis. Acad Emerg Med 2015;22:789–95.
  8. Kohn CG, Mearns ES, Parker MW, et al. Prognostic accuracy of clinical prediction rules for early post-pulmonary embolism all-cause mortality: a bivariate meta-analysis. Chest 2015;147:1043–62.
  9. Aujesky D, Roy PM, Le Manach CP, et al. Validation of a model to predict adverse outcomes in patients with pulmonary embolism. Eur Heart J 2006;27:476–81.
  10. Aujesky D, Perrier A, Roy PM, et al. Validation of a clinical prognostic model to identify low-risk patients with pulmonary embolism. J Intern Med 2007;261:597–604.
  11. Jimenez D, Yusen RD, Otero R, et al. Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy. Chest 2007;132:24–30.
  12. Donze J, Le Gal G, Fine MJ, et al. Prospective validation of the Pulmonary Embolism Severity Index: a clinical prognostic model for pulmonary embolism. Thromb Haemost 2008;100:943–8.
  13. Jimenez D, Aujesky D, Moores L, et al. Simplification of the Pulmonary Embolism Severity Index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 2010;170:1383–9.
  14. Righini M, Roy PM, Meyer G, Verschuren F, Aujesky D, Le Gal G. The Simplified Pulmonary Embolism Severity Index (SPESI): validation of a clinical prognostic model for pulmonary embolism. J Thromb Haemost 2011;9:2115–7.
  15. Fermann GJ, Erkens PMG, Prins MH, et al. Treatment of pulmonary embolism with rivaroxaban: outcomes by simplified Pulmonary Embolism Severity Index Score from a post hoc analysis of the EINSTEIN PE study. Acad Emerg Med 2015;22:299–307.
  16. Wicki J, Perrier A, Perneger TV, Bounameaux H, Junod AF. Predicting adverse outcome in patients with acute pulmonary embolism: a risk score. Thromb Haemost 2000;84:548–52.
  17. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med 2006;144:165–71.
  18. Klok FA, Kruisman E, Spaan J, et al. Comparison of the revised Geneva score with the Wells rule for assessing clinical probability of pulmonary embolism. J Thromb Haemost 2008;6:40–4.
  19. Penaloza A, Verschuren F, Meyer G, et al. Comparison of the unstructured clinician gestalt, the wells score, and the revised Geneva score to estimate pretest probability for suspected pulmonary embolism. Ann Emerg Med 2013;62:117–1242.
  20. Ceriani E, Combescure C, Le Gal G, et al. Clinical prediction rules for pulmonary embolism: a systematic review and meta-analysis. J Thromb Haemost 2010;8:957–70.
  21. Paiva LV, Providencia RC, Barra SN, Faustino AC, Botelho AM, Marques AL. Cardiovascular risk assessment of pulmonary embolism with the GRACE risk score. Am J Cardiol 2013;111:425–31.
  22. Zondag W, Vingerhoets LM, Durian MF, et al. Hestia criteria can safely select patients with pulmonary embolism for outpatient treatment irrespective of right ventricular function. J Thromb Haemost 2013;11:686–92.
  23. Aujesky D, Mazzolai L, Hugli O, Perrier A. Outpatient treatment of PE. Swiss Med Wkly 2009;139:685–90.
  24. Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet 2011; 378:41–8.
  25. Vinson DR, Ballard DWMark DG, et al. Risk Stratifying emergency department patients with acute pulmonary embolism: does the simplified Pulmonary Embolism Severity Index perform as well as the original? Thromb Res 2016 Dec 148:1-8.
  26. Maestre A, Trujillo-Santos J, Riera-Mestre A, Jimenez D, DiMicco P. RIETE Investigators. Identification of low-risk patients with acute symptomatic pulmonary embolism for outpatient therapy. Ann Am Thorac Soc 2015;12:1122–9.
  27. Dresden SMitchell PRahimi L, et al.  Right ventricular dilatation on bedside echocardiography performed by emergency physicians aids in the diagnosis of pulmonary embolism. Ann Emerg Med. 2014 Jan;63(1):16-24.
  28. Goldhaber SZ. Echocardiography in the management of pulmonary embolism. Ann Intern Med. 2002 May 7;136(9):691-700.
  29. Rudoni RRJackson REGodfrey GWBonfiglio AXHussey MEHauser AM. Use of two-dimensional echocardiography for the diagnosis of pulmonary embolus. J Emerg Med. 1998 Jan-Feb;16(1):5-8.
  30. Taylor RA, Davis JLiu R, et al. Point-of-care focused cardiac ultrasound for prediction of pulmonary embolism adverse outcomes. J Emerg Med. 2013 Sep;45(3):392-9.
  31. Casazza FBongarzoni ACapozi AAgostoni O. Regional right ventricular dysfunction in acute pulmonary embolism and right ventricular infarction. Eur J Echocardiogr. 2005 Jan;6(1):11-4.
  32. Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet 2011; 378:41–8.
  33. Fang MC, Fan D, Sung S, et al. Outcomes in adults with acute pulmonary embolism who are discharged from emergency departments: the Cardiovascular Research Network Venous Thromboembolism Study. JAMA Intern Med 2015; 175:1060–2.
  34. Erkens PMG, Gandara E, Wells P, et al. Safety of outpatient treatment in acute pulmonary embolism. J Thromb Haemost 2010;8: 2412–7.
  35. Vinson DR, Zehtabchi S, Yealy DM. Can selected patients with newly diagnosed pulmonary embolism be safely treated without hospitalization? A systematic review. Ann Emerg Med 2012;60: 651–62.
  36. Jimenez D, Kopecna D, Tapson V, et al. Derivation and validation of multimarker prognostication for normotensive patients with acute symptomatic pulmonary embolism. Am J Respir Crit Care Med 2014;189:718–26.
  37. Singanayagam A, Scally C, Al-Khairalla MZ, et al. Are biomarkers additive to pulmonary embolism severity index for severity assessment in normotensive patients with acute pulmonary embolism? QJM 2011;104:125–31.
  38. Lega JC, Lacasse Y, Lakhal L, et al. Natriuretic peptides and troponins in pulmonary embolism: a meta-analysis. Thorax 2009;64: 869–75.

ABOUT THE AUTHORS

Brit Long, MD is an EM Chief Resident at San Antonio Uniformed Services Health Education Consortium.

Alex Koyfman, MD is a Clinical Assistant Professor of Emergency Medicine at UT Southwestern Medical Center and an Attending Physician at Parkland Memorial Hospital. He is also Editor-in-Chief for emDocs.

2 Comments

  1. As stated in the article …Only patients with subsegmental PE and no evidence of proximal DVT are eligible for outpatient risk stratification, per the ACCP guidelines.

    The patient described in the article is diagnosed with a left segmental pulmonary embolism, yet there is contemplation about outpatient management. This is not subsegmental. Please explain the apparent discrepancy.

Leave A Reply