Acute pulmonary embolism (PE) is a preventable and treatable condition with a wide range of clinical presentations and outcomes. The mortality rate for acute PE ranges from 2.3% for low-risk patients to 68.4% for high-risk patients with cardiac arrest [1,2]. High-risk PE accounts for a small proportion of PE, but immediate and vigorous treatment is required due to its high mortality. The primary cause of death in PE is right-heart failure due to acute pressure overload. In this sense, extracorporeal membrane oxygenation (ECMO) might be useful in high-risk PE patients by providing time for the recovery of pulmonary flow and maintaining the patient’s hemodynamic stability [3,4]. Recently, there has been increasing attention to the utilization of ECMO for high-risk PE. However, little is known about the patients that benefit from ECMO. In this study, we report our clinical experiences of high-risk PE patients who received ECMO.

We identified nine patients with acute high-risk PE with cardiac arrest who were treated with ECMO between January 2010 and December 2018. Baseline characteristics of the patients and risk factors of PE are shown in Table 1. The median age of the patients was 60 years (range, 22-76 years) and six patients (66.7%) were male. Most of the patients had no significant comorbidities. The risk factors of three provoked PE were surgery in two cases and trauma in one case. Among the other six patients with unprovoked PE, one patient had previous thromboembolism.

Table 2 summarizes the presentation of PE patients. The most common initial symptom was shortness of breath (n=6, 66.6%) followed by chest pain (n=2, 22.2%). Among the nine patients, six (66.7%) had a cardiac arrest in the hospital, and three (33.3%) had a cardiac arrest outside of the hospital. The median mean arterial pressure, heart rate, respiratory rate, and body temperature were 54 mm Hg (range, 0-119), 100 beats/min (range, 0-123), 22 breaths/min (range, 0-38), and 36.0°C (range, 35.1-36.8), respectively. The median APACHE II score was 28 (range, 14-41) and the median SAVE score was -11 (range, -18 to -2). All the nine patients were diagnosed with a CT angiography, and eight (88.9%) had a bilateral pulmonary embolism. Right ventricular strain on CT was seen in seven patients (77.8%).

All the nine patients received mechanical support with veno-arterial ECMO and the median ECMO duration of 1.1 days (range, 0.2-14.0 days). ECMO was performed by a cardiothoracic surgeon. Arterial catheter size ranged from 16 to 18 FR, and venous catheter size ranged from 20 to 22 FR. Heparin was used as an anticoagulation agent to maintain ECMO. The target activated partial thromboplastin time was from 50 to 80 seconds.

The most common complication of ECMO was bleeding (n=7, 77.8%), none of which required transfusion. There were four ECMO catheter insertion-site oozing cases. The others included hemoptysis, hematuria, and gastrointestinal bleeding. In one case of the survivors, a pseudoaneurysm due to ECMO-related vascular injury developed and surgery was required for management.

The overall 30-day mortality rate was 77.8%. Therapeutic procedures performed for the treatment of PE and outcomes of the total population are shown in Table 3. All the nine patients had cardiac arrest before ECMO application, and reperfusion therapy was performed after ECMO application. Among the six patients who had in-hospital cardiac arrest, one patient was bridged to systemic thrombolysis with tissue plasminogen activator followed by surgical embolectomy. Another patient underwent catheter thrombectomy for reperfusion, and the other four received ECMO as a sole therapy with systemic anticoagulation. Among the three patients who had out-of-hospital cardiac arrest, one patient was bridged to reperfusion therapy using systemic thrombolytics. And the others received ECMO with anticoagulation. Two survivors experienced in-hospital cardiac arrest and were treated with ECMO alone. The cause of death was a multiorgan failure due to cardiac arrest in five patients, and refractory shock despite ECMO support in two patients. There were no deaths related to complications from ECMO or reperfusion therapy. The time taken from first cardiac arrest to initiation of ECMO was shorter in survivors (median, 31 minutes; range, 30-32 minutes) than in non-survivors (median, 65 minutes; range, 33-482 minutes). The duration of CPR was also shorter in survivors (median, 8 minutes; range, 3-13 minutes) than in non-survivors (median, 31 minutes; range, 15-87 minutes).

The prognosis of high-risk PE has improved due to advances in diagnosis and management, but it is still a fatal disease, and optimal management is unclear [3,5,6]. In this case series, we reported data on nine patients who underwent ECMO due to pulmonary thromboembolism. Among the nine patients, one underwent systemic thrombolysis, one underwent catheter thrombectomy, one underwent systemic thrombolysis followed by surgical embolectomy, and six others received ECMO as a sole therapy with systemic anticoagulation. All the patients had cardiac arrest before ECMO application, and the overall 30-day mortality rate was 77.8%.

Considering the rarity of the disease and the difficulty in studying critically ill patients, the clinical outcomes of high-risk PE requiring ECMO are elusive. Recently, Stadlbauer et al. [7] reported the long-term outcome of 119 patients who received ECMO for high-risk PE with an acceptable quality of life, and the overall survival to hospital discharge was 45.4%, this is the largest single-center study. But survival rate varies from 47% to 95% in smaller case series (Table 4) [8-13]. On the other hand, our report shows a lower survival rate (22.2%) despite the low prevalence of underlying comorbidities.

Cardiac arrest is a major prognostic factor in high-risk PE patients, and the mortality rate rises to 70% if it occurs [14]. Recent case series studies also showed that the prognosis of high-risk PE patients tends was poorer when the cardiac arrest occurred before or during ECMO application (Table 4). In our report, all the patients received ECMO only after cardiac arrest, which explains the low survival rate.

In high-risk PE patients, maintaining hemodynamic stability and preventing cardiac arrest through early ECMO application may have a greater impact on survival than choosing the optimal reperfusion therapy. As previously known, in the recent case series, the choice of reperfusion therapy does not seem to be related to survival (Table 4) [3]. Although there may be selection bias, even ECMO alone strategy has repeatedly shown non-inferior results in various studies [4,10,12,13]. On the other hand, cardiac arrest, low blood pressure, and high lactate level before ECMO application were related to mortality [4,7,8,13]. In our case series, the most notable difference between the survivors and non-survivors was the interval between cardiac arrest and ECMO initiation. The time taken from first cardiac arrest to initiation of ECMO was shorter in survivors (median, 31 minutes; range, 30-32 minutes) than in non-survivors (median, 65 minutes; range, 33-482 minutes). Because right-heart failure and death occur in the early stage of acute PE, immediate ECMO application may be crucial for survival [15,16]. The two survivors in our study also used the ECMO alone strategy, and reperfusion therapy was not performed because hemodynamic stability was well maintained.

It is also important to identify PE quickly to maintain the patient’s hemodynamic stability through ECMO. Although we did not analyze the clinical pretest probability for PE in this study, we can assume that most of the patients would have been in the moderate or high-risk group, considering the patients’ risk factors, initial vital signs, and deep vein thrombosis prevalence (n=5, 55.6%). Earlier suspicion of PE would have made the diagnosis faster. Among the six patients who had in-hospital cardiac arrest, only one had clinical suspicion of PE before cardiac arrest. In two other patients, the time from admission to cardiac arrest was 249 minutes and 191 minutes, which might have been long enough to suspect pulmonary embolism. However, their symptom was underestimated, leading to a fatal result (Table 3). Accordingly, ECMO and other reperfusion therapy were done as a salvage intervention, with poor outcomes. The introduction of a multidisciplinary pulmonary embolism response team (PERT) is necessary to prevent delayed detection and diagnosis of PE.

The PERT has been tried for better management of moderate to severe PE [17,18]. It is generally composed of experts from different specialties, including pulmonology/critical care, cardiology, emergency medicine, and cardiac surgery interested in PE. The PERT can be activated in patients with confirmed or highly suspected PE and offers a real-time multidisciplinary discussion, decision-making, and plan execution. The PERT approach has not yet shown better outcomes, but it may bring positive results if the appropriate treatment strategy is applied [18-20]. Pasrija et al. [12] and Guliani et al. [13] adopted a strategy including aggressive, protocol-driven utilization of ECMO in patients with high-risk PE and reported good results with the survival of 95% and 76%, respectively. Based on these promising results, we may expect PERT to play a great role in responding to high-risk PE.

Since the introduction of PERT stems from the need for optimal application of newly developed promising therapeutic tools, it generally focuses on therapeutic approaches. Based on our experience, PERT composition with enhanced educational and diagnostic function to prevent delay in diagnosis may help to improve the PE survival rate by preventing delayed diagnosis.

The main limitation of this study is that it is difficult to generalize because the sample size was small. In addition, this study was conducted retrospectively in a single institution and might have a selection bias.

In conclusion, high-risk PE with cardiac arrest has a high mortality rate despite aggressive management with ECMO and reperfusion therapy. We report our clinical experiences of ECMO as hemodynamic support for cardiac arrest in patients with high-risk PE.