Discussion
Pulmonary embolism is the most serious clinical presentation of venous
thromboembolism and is associated with significant morbidity and
mortality. In particular, patients with acute high-risk PE defined as
cardiogenic shock and systemic hypotension, are at particularly
increased risk of early death, and require emergency treatment to
restore circulation14.
Current guidelines for high-risk PE treatment recommend primary
reperfusion therapy and the option of ECMO. However, these
recommendations might not be optimal for patients with poor prognoses
who are in cardiogenic shock or require CPR. Patients with collapsed
high-risk PE have an extremely high-risk mortality rate because
conventional CPR including chest compression is usually not effective
due to right ventricle outflow obstruction. The in-hospital mortality of
high-risk PE requiring CPR may reach 65%15.
The majority of deaths in patient presenting with circulatory collapse
occur within the first hour after the presentation, and rapid
therapeutic action is therefore essential to save lives(4,5). ECMO is the most convenient circulatory assist
method widely available and is the alternative of choice for treating
patients with high-risk PE with circulatory
collapse16. Resuscitation guidelines suggest therapy
with thrombolytics in patients with pulmonary embolism and cardiac
arrest; but, in case of refractory cardiac arrest, because of the
inherent risk of bleeding of systemic thrombolysis, no further survival
options can be offered to patients with treatment failure till
now17.
Catheter based interventions is recommended for patients with
cardiogenic shock due to high-risk PE, and its equivalent to surgical
embolectomy18. Furthermore, catheter interventions
during CPR has been performed successfully in a small number of
patients19.
ECMO is recommended to provide pulmonary and circulatory support for the
emergency treatment of patients with massive pulmonary embolism and
cardiac arrest. It provides the ability to decompress the acutely
overloaded right atrium and ventricle, increase the aortic pressure and
myocardial blood flow, reverse ischemia and consequently improve the
right ventricular function. Many publications have 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 (20-21).
Similarly, in patients with high-risk PE, ECMO can function as an
adjunct to anticoagulation as a bridge to invasive management, such as
surgical embolectomy or CDT; or, as post-procedural support for patients
undergoing these therapies. Yusuff and colleagues, conducted a
systematic review of the literature on ECMO in patients with high-risk
PE. There were no randomized control trials, however, they reviewed over
20 years of case reports on the topic and found an overall survival of
70.1%. They did note that those who had ECMO initiated while in cardiac
arrest had an overall higher mortality compared with those who never
experienced such an event22.
To our knowledge, our series represents the largest review of VA-ECMO as
an adjunct to EKOS APT for high-risk PE treatment reported in the
literature. Although multiple case reports and series have previously
demonstrated the use of ECMO for massive PE, published mortality rates
have been prohibitive over long study periods (23,24).
Hashiba et al have reported that the ECMO survival rate at discharge was
83.3%. The outcome could be attributable to lower proportions of
patients with cardiac arrest, compared with our study
population25. Maggio et al have found that the
survival rate of ECMO for massive PE was 13 of 21 or 62%. However, only
8 of 21 patients experienced cardiac arrest, which was a smaller
percentage than in our study26.
Recently, Meneveau et al published the largest multicenter series of
high-risk PE patients
with refractory cardiogenic shock or cardiac arrest undergoing
ECMO27. The overall mortality rate was 61.5% in
high-risk PE patients who receive ECMO, especially in those with failed
fibrinolysis and in those with no reperfusion treatment. In patients
undergoing ECMO, 30-day mortality was 76.5% (13/17) for ECMO +
fibrinolysis and 77.8% (14/18) for ECMO alone. They concluded that ECMO
does not appear justified as a stand-alone treatment strategy in
high-risk PE patients with cardiogenic shock, but shows promise as a
complement to another reperfusion treatment such as surgical embolectomy
or CDT. Conversely to our study, Meneveau and colleagues did not assess
the potential role of catheter directed treatments in association with
ECMO in their patient cohort. There may be unstable, severely ill
patients who are not suitable for the intervention, or center who do not
have experienced interventionalist or surgical facilities on site.
However, they also concluded that, catheter-based interventions could be
a useful alternative that would make it possible to reduce the time
delay between onset and pulmonary reperfusion, by combining the
initiation of circulatory assistance with percutaneous treatments within
the same procedure. Recent data have shown promising results regarding
the safety and efficacy of this type of procedure in patients with
intermediate and/or high-risk PE28.
Dolmatova and colleagues described a series of 5 patients over 5 years,
with a 60% survival. In that group’s series, ECMO was used as a salvage
therapy in 4 of 5 patients after other therapies failed, with a 50%
mortality rate in this subset29. They also concluded
that ECMO may be reasonable to initiate in patients with a high-risk PE
who would otherwise be expected to die. However, our study contradicts
the opinion of using ECMO as a salvage therapy. Because, with early and
aggressive use of ECMO in conjunction with EKOS APT, we demonstrated a
75.9% survival rate for patients with a high-risk PE who had
cardiopulmonary arrest and required CPR. We believe that early
restoration of adequate perfusion limits ischemia, mitigates permanent
end-organ damage, and prevents initial or recurrent cardiac arrest in
this critically ill group of patients.
The clinical status of the survivor patients in our study, markedly
improved from time of cannulation to definitive intervention. Lactate,
pH, and bicarbonate levels all normalized. We also found that, in nearly
all cases, patients who survived to hospital discharge had normal RV
parameters on follow-up echocardiogram. Patients required a considerably
lower dose of inotropic/vasopressor agents, and SOFA scores notably
improved, indicating a lower predicted intensive care unit rate of
mortality after successful catheter-based intervention with the support
of VA- ECMO.
APT with EKOS system enhances CDT by accelerating the fibrinolytic
process via the application of ultrasound. Improving the efficiency of
the thrombolytic process reduces the treatment time and total lytic dose
delivered. The risk of an associated bleeding complication, which is
extremely increased by the concomitant ECMO procedure, is, therefore,
reduced31. Kuo et al reported a high pooled clinical
success rate of 86.5% in 594 patients treated with various CDT
techniques30. The risks of major and minor
complications were low at 2.4% and 7.9%, respectively.
Although ECMO may be helpful in many patients who have a low chance of
surviving high-risk PE without hemodynamic support, it does come with
complications, in particular, major bleeding. Despite the high-risk of
bleeding due to ECMO and using thrombolytics, our major bleeding rate
was lower than reported elsewhere (6,32). In our study
only 8 (27.5%) patients had a moderate hemorrhage classified as GUSTO
≤2 with a median of 2 packed red-cell and 3 fresh-frozen plasma units
transfused.
An important consideration in percutaneous femoral access for V-A ECMO
is lower-extremity acute limb ischemia. In a retrospective study of 43
patients with femoral arterial cannulae on ECMO, there were no cases of
limb ischemia in patients with prophylactically placed SFA distal
perfusion cannulae; 21% of patients without such cannulae did develop
limb ischemia33. Our practice is to routinely place a
prophylactic distal perfusion cannula in the SFA. Therefore, in our
patient series, the patients did not demonstrate any signs of acute limb
ischemia.
The results of our study require carefully interpretation. First the
study was retrospective and single center experience. Second, the
present study did not have a comparative group of patients who were not
undergoing APT with the support of V-A ECMO. Furthermore, catheter-based
interventions necessitate skilled physicians as a member of
interdisciplinary team required for successful treatment of high-risk
PE.