1358863X17739697

739697
research-article2017
VMJ0010.1177/1358863X17739697Vascular MedicineAin et al.
Original Article
Extra-corporeal membrane oxygenation and
outcomes in massive pulmonary embolism:
Two eras at an urban tertiary care hospital
Vascular Medicine
1­–5
© The Author(s) 2017
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https://doi.org/10.1177/1358863X17739697
DOI: 10.1177/1358863X17739697
journals.sagepub.com/home/vmj
David L Ain1, Mazen Albaghdadi2, Jay Giri3, Farhad Abtahian4,
Michael R Jaff5, Kenneth Rosenfield6, Nathalie Roy6,
Mauricio Villavicencio-Theoduloz6, Thoralf Sundt7
and Ido Weinberg6
Abstract
Mortality associated with high-risk pulmonary embolism (PE) remains high. Extra-corporeal membrane oxygenation
(ECMO) allows for acute hemodynamic stabilization and potentially for administration of other disease process altering
therapies. We sought to compare two eras: pre-ECMO and post-ECMO in relation to high-risk PE treatment and
mortality. A single-center retrospective chart review was conducted of high-risk PE patients. High-risk PE was defined as
acute PE and cardiac arrest or shock. A total of 60 patients were identified, 31 in the pre-ECMO era and 29 in the postECMO era. Mean age was 56.1±21.1 years and 51.7% were women. More patients in the post-ECMO era were identified
with computed tomography (82.8% vs 51.6%, p=0.011) and more patients in the post-ECMO era had right ventricular
dysfunction on echocardiography (96.4% vs 78.3%, p=0.045). No other differences were noted in baseline characteristics
or clinical, laboratory and imaging data between the two groups. In total, ECMO was used in 13 (44.8%) patients in
the post-ECMO era. There was greater utilization of catheter-directed therapies in the post-ECMO era compared
to the pre-ECMO era (n = 7 (24.1%) vs n = 1 (3.2%), p=0.024). Thirty-day survival increased from 17.2% in patients
who presented in the pre-ECMO era to 41.4% in the post-ECMO era (p=0.043). While more work is necessary to
better identify those PE patients who stand to benefit from mechanical circulatory support, our findings have important
implications for the management of such patients.
Keywords
extra-corporeal membrane oxygenation (ECMO), outcomes, pulmonary embolism (PE)
Introduction
The mortality associated with high-risk pulmonary embolism
(PE) has been reported to be as high as 70%.1 This high mortality is a result of acute hemodynamic decompensation,
which is primarily caused by an acutely failing right ventricle.2 Current treatment standards for high-risk PE may include
thrombolytic therapy (either systemic or catheter based), various catheter based clot-retrieval techniques, emergent
embolectomy and hemodynamic support.3 As hemodynamic
improvement is not often immediate after treatment for highrisk PE, extra-corporeal membrane oxygenation (ECMO) has
been suggested for cardiopulmonary support either as a
bridge to therapy or as support after therapy.4–12 Through
bypass of the failing right ventricle and lungs, ECMO maintains cardiac output and mitigates end-organ damage while
definitive PE treatment is undertaken. Utilization of ECMO
may allow for aggressive treatment of high-risk PE – including administration of thrombolytic medications, catheterdirected interventions, and surgical embolectomy.
Emerging but limited data suggest that aggressive management of high-risk PE, including the institution of
ECMO, may improve morbidity and mortality in massive
PE.4–12 Thus, ECMO has been employed in our institution
with the aim of improving hemodynamic parameters and
clinical outcomes in patients with high-risk PE.
1Cardiovascular
Medicine, Penn Medicine, Philadelphia, PA, USA
Northwestern Univeristy, Chicago, IL, USA
3Cardiovascular Medicine Division, University of Pennsylvania,
Philadelphia, PA, USA
4Cardiology, Sands Constellation Heart Institute, Rochester, NY, USA
5Administration, Newton-Wellesley Hospital, Newton, MA, USA
6Cardiology, Massachusetts General Hospital, Boston, MA, USA
7Thoracic Surgery, Massachusetts General Hospital, Boston, MA, USA
2Cardiology,
Corresponding author:
Ido Weinberg, Vascular Medicine, Massachusetts General Hospital, 55
Fruit St, GB 800, Boston, MA 02114, USA.
Email: [email protected]
2
Vascular Medicine 00(0)
Table 1. Demographic and comorbid conditions in patients with massive PE.
Age, years, mean ± SD
Sex, female, n (%)
Comorbidities
Surgery < 30 days, n (%)
Active malignancy, n (%)
Hypercoagulable disorder, n (%)
Coronary artery disease, n (%)
Cardiomyopathy / heart failure, n (%)
Hypertension, n (%)
Diabetes mellitus, n (%)
Renal failure, n (%)
Overall
(n=60)
Post-ECMO era
(2011–2014)
(n=29)
Pre-ECMO
(1994–2010)
(n=31)
p-value for ECMO/
pre-ECMO
56.1±21.1
31 (51.7%)
57.4±15.6
15 (51.7%)
54.8±25.4
16 (51.6%)
0.64
0.99
22 (36.7%)
16 (26.7%)
3 (5.0%)
5 (8.3%)
4 (6.7%)
26 (43.3%)
7 (11.7%)
1 (1.7%)
9 (31.0%)
8 (27.6%)
1 (3.4%)
0 (0%)
1 (3.4%)
11 (37.9%)
3 (10.3%)
1 (3.4%)
13 (41.9%)
8 (25.8%)
2 (6.5%)
5 (16.1%)
3 (9.7%)
15 (48.4%)
4 (12.9%)
0 (0%)
0.38
0.86
1.00
0.053
0.61
0.41
0.76
0.48
PE, pulmonary embolism; ECMO, extra-corporeal membrane oxygenation.
We therefore sought to compare treatment patterns and
outcomes of patients with high-risk PE treated at our institution before and after the implementation of ECMO in this
high-risk population.
Methods
The institutional review board of Partners Healthcare and
Massachusetts General Hospital approved the protocol.
All patients over age 18 years who were admitted to
Massachusetts General Hospital from 1 January 1994
through 31 December 2014, and who were assigned
International Classification of Diseases-9 codes for PE
(415.1 or 416.2) and cardiac arrest (427.5) or PE and
shock (785.5), were eligible for inclusion. A medical
records database query provided a list of subjects who
satisfied these criteria. To ensure selection of a uniform
patient population inclusive of only the sickest of PE
patients, we defined patients with acute PE and cardiac
arrest or shock as ‘high-risk’ and performed manual chart
review to verify eligibility for inclusion. Cases of presumed PE and non-thromboembolic pulmonary arterial
obstructive processes (e.g. amniotic fluid embolism)
were excluded. Detailed review of each medical record
was then performed to extract clinical details for analysis
(DLA).
Emergent ECMO began to be utilized for acute high-risk
PE at our institution around January 2011. We therefore
identified two groups of patients with high-risk PE for
comparison: those from the pre-ECMO era, from 1994 to
2010, when ECMO was not widely utilized for the management of patients with decompensated PE, and those from
the post-ECMO, aggressive era, 2011 until 2014, with
24-hour ECMO availability.
Descriptive statistics were used to report the various
variables. Between-group differences in patient characteristics were evaluated by using the chi-squared and
Fisher’s exact tests for categorical variables, t-tests and
Wilcoxon rank sum tests for continuous variables. A twosided p-value less than 0.05 was considered statistically
significant.
Results
Sixty subjects (31 women, 51.7%) with a mean age of 56.1±
21.1 years were included in the study. Table 1 shows patient
demographics and comorbid conditions, and Table 2 shows
the clinical, imaging, and laboratory data at the time of presentation. There was a trend towards increased prevalence of
coronary artery disease in the pre-ECMO era (16.1% vs 0%,
p=0.053). More patients in the post-ECMO era were diagnosed by computed tomography (CT) (82.8% vs 51.6%,
p=0.011). Otherwise there were no differences in baseline
characteristics between the pre- and post-ECMO groups.
Overall, 31 subjects with high-risk PE were treated
between 1994 and 2010 during the pre-ECMO era, and 29
were treated in the post-ECMO era. The average systolic
blood pressure was 70.6 mmHg, the average heart rate was
107.6 beats/min, and the average oxygen saturation was
80.8%. As expected for this patient population, right ventricular (RV) dysfunction was present in 88.2% of patients who
were assessed with echocardiography, and blood pressure
was supported with vasopressors in 92.5% of patients. More
patients in the post-ECMO era had echocardiographic evidence of RV dysfunction (96.4% vs 78.3%, p=0.045). In total,
ECMO was employed in 13 (44.8%) patients in the postECMO era versus none in the pre-ECMO era. Otherwise, no
differences were detected between patients in the two eras.
All patients who received ECMO were cannulated within
the first day of presentation; the average time from presentation to cannulation was 6 hours (range 2.4 to 22.3 hours).
Seven patients were cannulated in the operating room, one in
the cardiac catheterization laboratory, and five in other locations, such as the emergency department or intensive care
unit. Nine patients received peripheral veno-arterial ECMO,
while four received central veno-arterial support. The average length of ECMO support was 4 days. In nine patients,
ECMO was instituted before the definitive therapy. In the
remaining four cases, ECMO was started after surgical
embolectomy; in each of these cases, ECMO was started in
the operating room, immediately following embolectomy.
Table 3 shows the treatment modalities utilized in these
patients. All patients who received ECMO also received
invasive PE-related treatment, either catheter-directed
3
Ain et al.
Table 2. Clinical, imaging, and laboratory data at the time of presentation in patients with massive PE.
Clinical measures
Systolic BP, mean ± SD
Diastolic BP, mean ± SD
Heart rate, mean ± SD
SpO2, mean ± SD
Vasopressor therapy, n (%)
Number of vasopressors, n [IQR]
Imaging
PE location
Saddle, n (%)
Bilateral main PA, n (%)
Unilateral main PA, n (%)
Any segmental, n (%)
PE diagnosis by CT, n (%)
RV dilation by CT, n (%)
RV dysfunction by TTE, n (%)
PASP by TTE, mean ± SD
Laboratory data
Troponin T, mean ± SD
NT-proBNP, mean ± SD
Hematocrit, mean ± SD
Creatinine, mean ± SD
Overall (n=60)
Post-ECMO era
(2011–2014)
(n=29)
Pre-ECMO
(1994–2010)
(n=31)
p-value for ECMO/
pre-ECMO
70.6±50.1
41.0±33.9
107.6±42.6
80.8±14.1
49/53 (92.5%)
2.0 [1.0–3.0]
77.7±45.5
45.8±30.9
111.7±43.0
78.9±14.7
27 (93.1%)
2.0 [2.0–3.0]
63.2±54.5
35.4±37.3
101.2±42.4
83.6±13.3
22/24 (91.7%)
2.0 [1.0–2.0]
0.31
0.36
0.43
0.39
0.84
0.27
16 (26.7%)
10 (16.7%)
10 (16.7%)
22 (36.7%)
40 (66.7%)
18/30 (60%)
45/51 (88.2%)
50.3±19.2
10 (34.5%)
4 (13.8%)
6 (20.7%)
9 (31.0%)
24 (82.8%)
11/20 (55%)
27/28 (96.4%)
53.8±19.7
6 (19.4%)
6 (19.4%)
4 (12.9%)
13 (41.9%)
16 (51.6%)
7/10 (70%)
18/23 (78.3%)
45.7±18.2
0.47
0.9±1.3
5390.4±11905.8
35.3±6.7
1.40±0.97
0.6±0.7
7387.1±14562.2
36.3±6.6
1.51±1.36
1.2±1.7
1796.4±1537.7
34.3±6.8
1.29±0.34
0.13
0.24
0.26
0.38
0.011
0.43
0.05
0.24
BP, blood pressure; CT, computed tomography; ECMO, extra-corporeal membrane oxygenation; IQR, interquartile range; NT-proBNP, N-terminal
of the prohormone brain natriuretic peptide; PA, pulmonary artery; PASP, pulmonary arterial systolic pressure; PE, pulmonary embolism; RV, right
ventricular; SpO2, peripheral capillary oxygen saturation; TTE, transthoracic echocardiography.
Table 3. Treatment modalities employed in patients with massive PE.
Treatment
ECMO, n (%)
Anticoagulation
Intravenous thrombolysis, n (%)
Catheter-directed therapy, n (%)
Surgical embolectomy, n (%)
Overall (n=60)a
Post-ECMO era
(2011–2014)
(n=29)a
Pre-ECMO
(1994–2010)
(n=31)a
p-value for ECMO/
pre-ECMO
13 (21.7%)
19 (31.7%)
13 (21.7%)
8 (13.3%)
13 (21.7%)
13 (44.8%)
10 (34.4%)
2 (6.9%)
7 (24.1%)
9 (31%)
0 (0%)
9 (29%)
11 (35.5%)
1 (3.2%)
4 (12.5%)
<0.0001
0.78
0.011
0.024
0.12
PE, pulmonary embolism; ECMO, extra-corporeal membrane oxygenation.
aSome patients received more than one treatment.
therapies or surgical embolectomy, and there was overall
greater utilization of catheter-directed therapies in the postECMO era compared to the pre-ECMO era (n = 7 (24.1%)
vs n = 1 (3.2%), p=0.024).
Thirty-day survival increased from 17.2% in patients who
presented in the pre-ECMO era to 41.4% in the post-ECMO
era (p=0.043). Numerically, there was also improved 1-year
survival in the post-ECMO era, although this did not achieve
statistical significance (30.8% vs 17.2%).
Discussion
These findings suggest that the implementation of a program
to aggressively manage patients with PE and shock or cardiac
arrest, which includes the 24-hour availability of ECMO,
may improve survival. While causality cannot be inferred
between the introduction of ECMO and patient outcomes,
examination of our results suggests a plausible explanation
for the improved survival with the implementation of ECMO
for massive PE complicated by shock or cardiac arrest.
By stabilizing hemodynamic parameters and improving
oxygenation, ECMO can serve as a bridge to other therapies as well as to recovery. An overall more aggressive
approach to high-risk PE was likely permitted by ECMO
support. This includes surgical embolectomy and catheterdirected thrombolysis, both of which were utilized more
frequently in the post-ECMO era, as well as overall intensive medical care. Thus, perhaps the intervention we examined in the present study is best thought of as ‘ECMO and
all subsequent treatment permitted by ECMO’.
4
As there are many unknowns in the care of PE patients,
a team-based approach to these patients has been gaining
popularity. Dubbed ‘PERT’ (PE Response Teams), complex patient care is addressed by several relevant specialists
including, but not limited to, interventional cardiology, vascular medicine, hematology, radiology, pulmonary and
critical care, and cardiothoracic surgery.13 While these
events do not correlate temporally with the advent of
ECMO in our institution, they have been utilized to streamline the utilization of resources for the benefit of the most
difficult to treat PE patients.3
Notwithstanding, coincidental with the availability of
ECMO, a more aggressive approach to the treatment of PE
was undertaken, suggesting that some of these therapies
may have been facilitated by ECMO support. Work published over the latter half of the last decade has demonstrated that ECMO has a role as a bridge to percutaneous
coronary intervention in patients with acute coronary syndrome and cardiogenic shock, as well as in the treatment of
cardiogenic shock itself.14–16 Similarly, in patients with
high-risk PE, ECMO can function as an adjunct to anticoagulation or systemic thrombolysis; as a bridge to invasive
management, such as surgical embolectomy or catheterdirected therapies; or, as post-procedural support for
patients undergoing these therapies.
Supporting our findings, several case reports and small
case series have suggested that ECMO may have a role in
decreasing mortality in patients with massive PE.4–12 One
case series spanning 13 years included 21 patients with
massive PE, 13 of whom developed cardiogenic shock and
eight that had ongoing cardiac arrest. Thirteen of the 21
patients (62%) survived to 1 year.10 Another recent series
included four patients with massive or submassive PE who
had been aggressively managed before the institution of
ECMO. Three of these patients died during the index hospitalization. The authors of this case series caution that a
reporting bias likely exists in the literature, and suggest that
the mortality of patients with PE who are placed on ECMO
may be higher in practice than is suggested by case reports.6
Limitations
Our study is retrospective and limited by a small sample
size. However, to date, there have been no published data
comparing ECMO as part of the armamentarium for treatment of PE with standard care without ECMO support.
Furthermore, in relation to previous publications, our series
is comparatively large. While our analysis suggests that
ECMO use may be associated with improved mortality in
high-risk PE patients, we acknowledge the presence of confounders influencing this association, particularly the more
generalized use of more aggressive therapies in our ECMO
era. Thus, ECMO was only viewed as part of a more generalized approach to these patients.
Conclusion
In conclusion, our hypothesis-generating study demonstrates an increase in 30-day survival among patients with
cardiac arrest or shock resulting from PE who were treated
Vascular Medicine 00(0)
once an aggressive PE treatment program, including ECMO
and other invasive therapies, was instituted. While more
work is necessary to better identify those patients who
stand to benefit from mechanical circulatory support, our
findings have important implications for the management
of such patients.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
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