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.