Discussion
Extracorporeal life support has been proposed as an emerging rescue therapy in cases of refractory cardiac arrest. The Extracorporeal Life Support Organization (ELSO, Ann Arbor, MI, USA) and the American Heart Association (AHA, Dallas, TX, USA) also recommend that ECPR should be considered in selected patients.18-21 Previous studies have reported that in-hospital cardiac arrest (IHCA), duration of pre-ECPR resuscitation, and etiology of cardiac arrest are prognostic factors.22 Several studies related to post-ECPR care focused on improving neurologic outcomes.8-10, 23 This present study was the first study that investigated predictive factors for successful weaning off ECMO support by analyzing parameters of pre-, intra-, and post-ECPR.
Long CPR duration and loss of pulse pressure were identified as independent risk factors of unsuccessful weaning off ECMO support after ECPR. Previous studies have demonstrated that shorter low-flow time increases survival rate after ECPR in both IHCA and OHCA,5, 6 and our results confirmed the risk of unsuccessful weaning off ECMO support after ECPR.5-10, 22
We consider that loss of pulse pressure after ECPR is a risk factor worth emphasizing. In patients that lost pulse pressure after ECPR, the probability of successful weaning off ECMO support was reduced. In fact, loss of pulse pressure was the only prognostic factor related to post-ECPR management. Although pulse pressure may disappear due to severe impairment of the LV after ECPR, and a non-contractile LV can dilate and lead to pulmonary edema or LV thrombosis. Even when full support of ECMO is provided, blood supplied from the bronchial artery, pulmonary and coronary circulations can cause left heart dilation leading to left ventricular myocardium injury. LV dilation also increases myocardial oxygen consumption and delays cardiac restoration particularly in the setting of AMI,24 and this might form a vicious cycle due to aggravation of loss of pulse pressure by LV injury.
Furthermore, substantial enhancement of intravenous volume is required to maintain full ECMO support as pulmonary edema and hemorrhage could reduce intravascular volume. In addition, systemic ischemia and reperfusion response after resumption of spontaneous circulation from cardiac arrest cause systemic inflammatory response of the immune system and coagulation.25 Clinical manifestations of this include intravascular volume depletion, impaired vasoregulation and impaired oxygen delivery. The first priority for hemodynamic stabilization after CPR is the optimization of right-heart filling pressures using intravenous fluids.23, 25 Furthermore, intravenous volume replacement after ECPR may greater than that required after CPR because extracorporeal circulation could exacerbate systemic inflammatory responses and intravascular volume depletion. Also, loss of pulse pressure might lead to excessive volume replacement to maintain ECMO flow, which aggravates the systemic inflammatory responses. Our findings indicate that loss of pulse pressure after ECPR might trigger this vicious cycle. This hypothesis might explain that loss of pulse pressure is an unfavorable factor for weaning off ECMO support after ECPR.
Post-cardiac arrest myocardial dysfunction also contributes to loss of pulse pressure. Due to the small sample size, this study could not distinguish a bias that weaning off ECMO support was unsuccessful, because myocardial dysfunction of patients with loss of pulse pressure was more severe. Nevertheless, the study does demonstrate that patients with loss of pulse pressure after ECPR should receive more careful monitoring and management to facilitate successfully weaning off ECMO support. Although our subgroup analysis did not show left heart decompression had a significant effect, left heart decompression, such as LA venting and Impella (Abiomed, Danvers, MA), might help reduce injury caused by LV dilation and pulmonary edema.23, 26-28 At our center, left heart decompression is performed when pulmonary edema was aggravated after ECPR regardless of pulse pressure. Furthermore, we infuse inotropes related to heart rate, such as isoproterenol and dobutamine, to patients with reduced pulse pressure to help maintain pulse pressure. Temporary pacing might help maintain pulse pressure as well. Reducing the afterload burden of ECMO may also have an important contributory effect to maintain pulse pressure. When pulse pressure is lost, full ECMO support may be necessary to maintain organ perfusion, and when satisfactory, probably increases the likelihood of patient recovery.
According to several studies conducted on pulsatile ECMO model, pulsatile ECMO generates more hemodynamic energy than nonpulsatile ECMO and improves clinical outcomes.13, 14 Previous reports have demonstrated that pulsatile flow reduces systemic vascular resistance and hypothyroidism and improves catecholamine response, gastrointestinal perfusion, myocardial blood flow, and clinical outcomes.29-34 Although physiologies associated with pulsatile extracorporeal circulation and the maintenance of pulse pressure cannot be directly compared, conceptually maintaining pulse pressure would appear to have a positive effect on successfully weaning off ECMO support after ECPR. Although continuous-flow left ventricular assist devices (CFVAD) are now the most widely used because they are smaller, more reliable, and more durable than pulsatile-flow left ventricular assist devices (PFVAD), there is research that PFVAD might have potential advantages due to natural physiology.35 Maintenance of pulse pressure after ECPR should be considered for successful weaning off ECMO after ECPR like as the physiology of pulsatile ECMO or PFVAD.