Contemporary Pulmonary Embolism Management Part II: Safe Discharge Home of Low-Risk Acute PE Patients

Ken Milne, MD

In part 1 of this essay, we described the process of building a community-wide consensus diagnostic algorithm using clinical decision instruments within the context of reducing the over-testing/over-diagnosis phenomenon with pulmonary embolism (PE). In part 2, we explore the once unthinkable disposition decision — discharging low-risk PE patients to home from the ED. After the diagnosis of PE is established the reflexive disposition has been hospital admission in the United States (U.S.) for 50 years, but not elsewhere around the world where the majority of PE patients are managed as an outpatient from the ED. We describe an evidence-based protocol devised with hospitalists to enable safe, reliable outpatient management for many PE patients.

Reducing PE Admission Rates Using Evidence- and Consensus-Based Protocol

Per-patient inpatient admission costs for PE in the United States ranged from $25,000 to $44,000 between 1998 and 2006 (Park 2009). For more accurate risk-stratification, some suggest even moreED-based testing of PE patients “using a thoughtful approach,” including troponin (Moores 2010), ECG (Abecasis 2008), BNP (Aqterof 2010), and echocardiography (Borloz 2011) as surrogate markers of right ventricular strain. However, the subset of PE patients who benefit from additional testing remains undefined and could lead us down yet another path towards overtesting →overdiagnosis → overtreatment, so this is not currently a strategy that is ready for prime time.

At least two PE risk stratification instruments exist. With the intent to safely reduce PE admission rates once PE was diagnosed, we use the Pulmonary Embolism Severity Index (PESI, see Aujesky 2005) based upon current evidence (Donzé 2008, Choi 2009) and in order to replicate the highest quality ED-based outpatient PE management evidence trials. The PESI can be computed online (see link on the Figure) and consists of the following questions:

Score

1. Patient Age
2. Male Patient
3. History of cancer
4. History of heart failure
5. History of chronic lung disease
6. Heart rate ≥ 110
7. Systolic BP < 100 mm Hg
8. Respiratory rate ≥ 30
9. Temperature ❤6°C/96.8°F
10. Altered mental status
11. Room air O2 saturation < 90%

1 point per year
+10
+30
+10
+10
+20
+30
+20
+20
+60
+20

The PESI Score predicts 30-day PE-related mortality.

ScoreClass 30-day PE-related mortality≥ 65
66–85
86–105
106–125
>125

I
II
III
IV
V

0–1.6%
1.7%-3.5%
3.2%-7.1%
4.0%-11.4%
10.0%-24.5%

If a subset of PE patients are to be discharged home, PESI Class I patients are the most obvious target.

Is Outpatient PE Management Safe and Effective?

ED physicians currently discharge 1% of PE patients, but are asked to do so by admitting services in 21% of cases (Kabrhel 2010). One recent systematic review (Vinson 2012) identified 8 studies that diagnosed acute PE and discharged a portion home. Seven of these studies were observational (i.e. not randomized controlled trials), only four included ED patients and only one included U.S. patients. All of the studies had extensive exclusion criteria, including social factors (living alone, indigent, lack of transportation for outpatient follow-up) that prohibited outpatient PE management — all of which are reflected in the protocol that we derived with hospitalists (see below). No cases of venous thromboembolism (VTE) or hemorrhage-related death were noted across seven studies with 90-day follow-up (0%, 95% CI 0–0.62%), while one study reported two deaths at 180-days (if this occurred at 90-days, estimated risk 0.26%, 95% CI 0–1%). Recurrent VTE ranged from 0–6.2% and non-fatal hemorrhage ranged from 0–1.2% at 90-days. Another systematic review published in 2013 (Piran 2013) confirms the safety of outpatient PE management, if home circumstances are adequate.

Since Rick questions the true value of meta-analyses (“three 2nd graders do not make a 6th grader”), it is worth looking more closely at one of the individual studies. The single randomized trial (Aujesky 2011) was an open-label non-inferiority trial across 19 EDs in four countries (including the U.S.) from 2007–2010. The authors included non-pregnant, PESI Class I or II patients without renal dysfunction, recent bleed or social issues. They hypothesized a non-inferiority margin of 4% and in the per-protocol analysis outpatient management was non-inferior to inpatient care for 90-day recurrent VTE (0.6% difference, upper limit of 95% CI 2.9%, p = 0.014). However, the upper limit of the confidence interval for major bleeding exceeded the 4% threshold at 90 days (3/163 = 1.8%, upper limit of 95% CI 4.5%) so outpatient PE management is not non-inferior to inpatient management with respect to major bleed risk. No major bleeds occurred in the inpatient group. The three major bleeds in the outpatient group were intramuscular hematomas on days 3 and 13 and one episode of menometrorrhagia on day 50. No differences in mortality were identified (0%, upper limit 95% CI 2.1%). No differences in patient satisfaction were observed between inpatient and outpatient management (92% outpatients versus 95% inpatients satisfied or very satisfied). Hospitalization time was 0.5 days in the outpatient group versus 3.9 days in the inpatient group.

All of the available studies used low-molecular-weight heparin + warfarin (not dabigatran or one of the other newer anticoagulation therapies) so this data cannot be extrapolated to these newer agents (Spyropoulos 2013). One preliminary industry-sponsored trial indicates that outpatient management with rivaroxaban is safe across a broad socioeconomic spectrum of patients (Beam 2015).

Ready for prime time or clear as mud? Certainly, emergency medicine needs to become more efficient and cost-conscious in the 21st century era of medicine. This two-part essay was meant to provide one diagnostic approach and one disposition algorithm to begin reducing over-testing and the downstream consequences for one condition using evidence-based diagnostics and implementation science ideas. Nonetheless, multiple uncertainties undoubtedly remain:

• Can and will EPs accurately and reliably risk stratify PE patients for imaging and outpatient management decisions (Leclercq 2004)?
• Which risk stratification instrument should be used?
• Is LMWH available to destitute ED patients 24/7?
• Who will provide LMWH teaching and is this instruction reliable?
• How will follow-up be assured and what QI process will close the loop?
• Hospitalists have suggested that future studies of outpatient PE management should evaluate whether inpatient is superior to outpatient, rather than whether outpatient management is non-inferior to admission.

In terms of facilitating shared decision making (Kanzaria 2015, Hess 2015) with PE patients who might be appropriate for outpatient management, one appropriate approach might be:

“A single moderate quality study from 19 EDs in Europe and the U.S. demonstrates that certain PE patients can be safely and effectively treated with blood thinners at home, although there is a chance of increased bleeding risk at 90 days (< 5% at most) with home management.”

Chris Carpenter, MD, MSC
W. Ken Milne, MD

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