Background
Acute, massive high-risk pulmonary embolism (PE) is defined as an embolus sufficiently obstructing pulmonary blood flow to cause right ventricular (RV) failure, hypoxemia, and hemodynamic instability [
1]. Although the epidemiology of massive PE is difficult to determine, it remains a significant cause of cardiovascular morbidity and mortality worldwide, with overall in-hospital mortality rates ranging from 25% for patients with cardiogenic shock to 65% for those requiring cardiopulmonary resuscitation [
1,
2]. The latest European guidelines enhance the clinical classification, based on the estimated PE-related early mortality risk, defined by in-hospital or 30-day mortality, with high-risk PE being suspected or confirmed in the presence of shock or persistent arterial hypotension [
3]. Treatment is based on bedside hemodynamic and respiratory support, unfractionated heparin infusion (UFH), and reperfusion therapy with systemic thrombolytic agents (class IB), surgical pulmonary embolectomy (class IC) or percutaneous catheter-directed thromboaspiration or embolectomy (class IIaC) [
3]. Because of contraindications or major clinical instability, a few patients are not amenable to reperfusion therapies or fail to improve after this treatment. For them, venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is one of the most reliable and quickest ways to decrease RV overload, improve RV function and hemodynamic status, and restore tissue oxygenation. Although ECMO is increasingly available and mobile ECMO teams, if locally available, can assure rapid deployment of this salvage therapy, ECMO data in this context are limited [
4‐
7]. We describe herein our tertiary-care center’s experience with VA-ECMO–treated patients with acute, massive, high-risk PE, and report their short- and long-term outcomes.
Discussion
To our knowledge, this is the largest follow-up study on VA-ECMO-treated life-threatening PE in the modern era. Despite extreme disease severity at ECMO implantation, multiorgan failure and 91% SAPS II-predicted mortality, 47% of these patients were alive at 90 days with acceptable long-term HRQOL. Nevertheless, after median 19-month follow-up, physical limitations were frequently reported, with normal mental health function. In addition, anxiety, depression or PTSD symptoms persisted for almost one-third of the survivors.
To date, literature on VA-ECMO, as rescue treatment for extremely severe, massive PE, had been limited to small case series or case reports with no long-term outcome evaluation see Additional file
3 (Table
3). In 2007, Maggio et al. reported on 21 cohort patients diagnosed with high-risk PE between 1992 and 2005 [
4]: 19 were cannulated with VA bypass, six received pre-ECMO thrombolytic therapy and eight were cannulated after suction or surgical pulmonary embolectomy failed. Overall survival was 62%, with catastrophic neurological events responsible for 50% of the deaths. In our study, severe bleeding episodes occurred in 15 (88%) patients requiring packed red-cell and/or fresh-frozen plasma transfusions. Major bleeding, including intracranial hemorrhage is a well-recognized ECMO complication [
25], with numerous identified risk factors, e.g., thrombocytopenia, vasopressor requirement, and cardiopulmonary resuscitation [
25,
26]. Due to previous thrombolytic treatment and curative anticoagulation, life-threatening PE on ECMO may carry additional risk factors of major bleeding during this circulatory support.
Table 3
Studies on patients with acute, massive, high-risk PE on VA-ECMO support included in the systematic review
| 1994–1998 | 7 | 71 | 0 | 100 | 3 surgical pulmonary embolectomies | 0 | 57 |
| 1992–2005 | 21a
| 38 | 6 suction and 2 surgical pulmonary embolectomies | 29 | 1 suction and 2 surgical pulmonary embolectomies | 4 catastrophic neurological events; 1 dislodged arterial cannula | 62 |
| 1983–2006 | 7 | NR | 0 | 86 | 1 suction and 1 surgical pulmonary embolectomies | NR | 57 |
| 2005–2011 | 4 | NR | 0 | 0 | 1 suction pulmonary embolectomy | None | 100 |
| 1992–2008 | 10 | 90 | 2 suction pulmonary embolectomies | 100 | 7 suction pulmonary embolectomies | 2 major bleeding | 70 |
| 2007–2011 | 4 | 50 | 1 suction and 2 surgical pulmonary embolectomies | 25 | None | NR | 25 |
| NR | 6 | 100 | None | 66 | 1 surgical pulmonary embolectomy | 3 major bleeding | 33 |
| 2008–2014 | 5 | 100 | None | 60 | 1 surgical pulmonary embolectomy | 1 major bleeding | 40 |
| 2000–2013 | 13 | NR | None | 15 | 11 surgical pulmonary embolectomies | NR | NR |
This study | 2006–2015 | 17 | 88 | 1 suction and 1 surgical pulmonary embolectomies | 47 | 1 suction and 1 surgical pulmonary embolectomies | 15 major bleeding | 47b
|
Our results highlight that ECMO can provide lifesaving hemodynamic support at bedside for critically ill patients too unstable to tolerate other interventions or refractory to other therapies. A recent survival-prediction model indicated a lower predicted chance of survival for each associated extracardiac organ failure at ECMO onset, which starkly illustrates the crucial impact of VA-ECMO timing for refractory cardiogenic shock [
27]. To shorten this interval, mobile ECMO teams able to implant a portable and quick-to-prime ECMO circuit just after the emergency call [
28] might help clinicians overcome these difficulties.
Current guidelines for high-risk PE advocate using reperfusion therapy with systemic thrombolytic agents or surgical pulmonary embolectomy [
3]. However, those recommendations might be questionable for the sickest patients in severe shock or cardiac arrest, when thrombolysis takes time to be effective and surgery is not immediately available. Therefore, VA-ECMO could be used to rescue patients when thrombolytic treatments fail or as temporary hemodynamic support prior to surgical [
29] or catheter-based embolectomy [
30]. However, surgical embolectomy is a major intervention requiring sternotomy and cardiopulmonary bypass that carries significant morbidity and mortality in this context of advanced shock and multiorgan failure; hence, VA-ECMO might also be used alone until heparin-induced and spontaneous endogenous thrombolysis permit weaning-off support [
5]. Herein, sufficient clot dissolution allowing ECMO removal was obtained within 4 (3–11) days for the eight patients rescued by VA-ECMO alone.
The other rationale supporting surgical thrombectomy on ECMO is to limit the CTEPH risk [
29], which has been reported to be 0.1–9.1% for patients within the first 2 years after symptomatic PE [
31]. However, data confirming that hypothesis are lacking. Notably, none of our long-term survivors developed CTEPH. In addition, despite significant mechanical PA obstruction by massive PE, thrombectomy to prevent CTEPH is not yet systematically advocated [
3]. The lack of linear correspondence between the degree of mechanical obstruction and CTEPH risk, because of concomitant small-vessel pulmonary arteriopathy [
32], makes the benefit of adding surgical thrombectomy in this context questionable. Lastly, a recent systematic review of case reports and case series published over the past 20 years found similar outcomes for patients who underwent surgical or catheter embolectomy or no additional therapies on ECMO [
7]. The benefit of mechanical removal therapies, e.g., catheter or surgical thrombectomy, over exclusive VA-ECMO use warrants further investigation.
Despite very severe disease at ECMO initiation, the 47% 90-day survival observed for our series is comparable with results reported in studies included in our systematic review (Table
3) and with the 42% hospital-survival rate of a large international cohort of ECMO-treated refractory cardiogenic shock patients [
27]. Despite high numbers of our patients with pre-ECMO cardiac arrest or cannulated during cardiopulmonary resuscitation, our survivors’ survival rate was also higher than those reported for ECMO-treated in- and out-of-hospital cardiac arrest (28.8% and 4%, respectively) [
33,
34]. However, HRQOL evaluated after median 19-month follow-up, was still impaired, compared to sex- and age-matched controls, especially concerning SF-36 physical health and social-functioning domains, while general and mental health were considered satisfactory. Although, case-mix differences make comparisons between series difficult, we observed than our extremely ill patients’ SF-36 scores were similar to those of both ECMO-assisted refractory shock [
22] and ECMO-treated refractory ARDS patients [
23]. Nevertheless, the burden of ECMO-induced physical limitations for our ECMO-treated survivors was still perceptible 19 months post-hospital discharge with back-to-work impact. Although thoroughly described in previous case series [
8‐
10], ECMO-related long-term physical sequelae have not been investigated. Future studies are warranted to prevent these complications and improve their long-term management.
Our study’s strengths are the larger number of consecutive patients included and their detailed characterization, and its longitudinal design with median survivor follow-up 19 months post-ICU discharge. However, our study also has limitations. First, it is a retrospective, single-center study. Second, the self-assessed persistently impaired physical health and vitality might not be specific to PE but may represent sequelae of any severe disease requiring prolonged ICU stay and ECMO, including critical illness, muscle wasting, and weakness. Third, we did not perform protocolized follow-up based on long-term cardiac echocardiography and imaging to detect CTEPH development. Further studies focusing on this point are needed to support long-term safety of an ECMO strategy without additional mechanical clot-removal therapies. Lastly, PE diagnosis was confirmed in 15 out of the 17 patients. The remaining two patients had high massive PE suspicion but died within 24 hours after ICU admission without chest CT scan performed. The family refused autopsy. However, they both had prolonged cardiac arrest with massive RV dilatation on cardiac echocardiography, predisposing factors for venous thromboembolism, and no evidence of right myocardial infarction.