In this case report, we described our experience in the successful management of hemodynamic deterioration secondary to SPE-induced cardiac arrest using VA-ECMO with adjusted-dose systemic anticoagulation in a lung cancer patient with brain metastases. The patient had no clotting or bleeding complications during VA-ECMO treatment and was discharged from the hospital with good neurological function. This case suggests the effectiveness of VA-ECMO as a salvage therapy for SPE-induced hemodynamic collapse in malignancy patients with brain metastases.
To our knowledge, there is a scarcity of case reports on the application of VA-ECMO to successfully rescue SPE-induced hemodynamic collapse in advanced malignancy patients with brain metastases. Indeed, ECMO is infrequently applied in the cohort of patients with advanced malignancy, especially those with brain metastases. According to the latest report from the extracorporeal life support organization registry, the percentage of ECMO runs for neoplasms is around 3% of all ECMO runs, and ECMO runs for the central nervous system neoplasms account for only 1.3% of all ECMO runs for neoplasms [9]. The extremely reduced utilization of ECMO in the population of advanced malignancy with brain metastases might attribute to the following potential reasons: first, the long-term prognosis of a patient with advanced malignancy receiving ECMO may be undesirable; second, the potential ECMO-related bleeding complications were frequent and, sometimes, lethal [11, 12]. Hence, when a malignancy patient with brain metastases developed respiratory failure or circulatory shock, his/her relatives or physicians in charge might abandon the option of ECMO treatment in consideration of the high cost and uncertain prognosis. Cost-effectiveness has always been an important factor that relatives or physicians have to consider before establishing an ECMO circuit. Several studies reported that VA-ECMO was a cost-effective treatment for cardiogenic shock, cardiac arrest, or cardiotoxicity poisonings [13,14,15,16]. However, there was no study investigating the cost-effectiveness of VA-ECMO in the special subgroup population (i.e., malignancy) so far. Despite this, we believe that VA-ECMO remains a cost-effective treatment for PE-induced refractory shock in patients with malignancy, provided that strict indications and contraindications are applied while respecting the relatives' willingness to rescue. Based on the experience of our ECMO center, we are still willing to discuss with the relatives the possibility of applying ECMO to treat acute hemodynamic instability in malignancy patients, as long as their basic nutritional status is good and has not progressed to cachexia.
Despite the above-mentioned adverse factors, VA-ECMO seems to manifest expected survival benefits in the treatment of massive PE-induced circulatory instability. Most recently, a retrospective large-scale study suggested that compared to thrombolysis alone, VA-ECMO treatment alone or as part of conventional reperfusion therapy offered survival benefits in patients with PE deteriorating to cardiac arrest [17]. Regarding the reperfusion therapy for acute PE in malignancy patients with brain metastases, surgical pulmonary embolectomy or percutaneous catheter-directed treatment is preferred to thrombolysis due to the high risk of bleeding [5]. However, the patient in this case report received a half-dose of rtPA (50 mg over 2 h) for reperfusion therapy because our hospital could not provide mature embolectomy or percutaneous catheter-directed treatment. The efficacy and safety of a half-dose regimen of rtPA were confirmed in a multicenter randomized controlled trial [18], which suggested that a half-dose regimen of rtPA, compared with the usual dose (100 mg), exhibited similar efficacy and perhaps better safety (less bleeding) in patients with acute PE. Finally, the patient in our case report was successfully managed with VA-ECMO for SPE-induced hemodynamic instability and was alive at discharge from the hospital with good neurological function, without any bleeding complications. This case report provides an important clinical implication that a half-dose regimen of rtPA combined with VA-ECMO may be a salvage therapy that is worthy of consideration for advanced malignancy patients with brain metastases who suffered severe SPE-induced circulatory shock, particularly in those hospitals that cannot provide embolectomy or thrombectomy. However, it should be recognized that this report only includes a single case, which represents a primary limitation, thus the results should be interpreted with caution in clinical practice.
Thrombotic events and bleeding complications during ECMO runs are two major contradictory issues encountered by clinicians. Systemic anticoagulation with unfractionated heparin, the most frequently used anticoagulant [19], will be inevitability accompanied by an increased risk of bleeding. A recent systematic review and meta-analysis summarized that bleeding complications occurred in 8–100% of the included patients and neurological complications (including neurological bleeding) in 8–76% of the included patients [20]. It is thus indispensable to adjust the infused dose of unfractionated heparin based on individualization. A previous study demonstrated the safety of a low-dose anticoagulation strategy including the maintenance of aPTT of 40–60 s during ECMO therapy for acute respiratory distress syndrome [21]. Therefore, we adjusted the dose of unfractionated heparin to maintain a targeted ACT range of 150–170 s and an aPTT of 40–60 s to avoid ICH given the brain metastases. Finally, the patient had no clotting or bleeding complications during VA-ECMO treatment.
In conclusion, VA-ECMO may be an effective ‘bridging’ therapy to circulation recovery during conventional reperfusion therapy for SPE-induced hemodynamic collapse in malignancy patients with brain metastases. Given the high risk of bleeding in this population cohort, an individualized anticoagulation regimen is suggested.