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Corresponding author: Tommaso Scquizzato, Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60 – 20132, Milan, Italy, Tel +39 02 2643 6158; Fax +39 02 2643 6152
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
Extracorporeal cardiopulmonary resuscitation (E-CPR) is the establishment of veno-arterial extracorporeal membrane oxygenation (ECMO) during ongoing cardiopulmonary resuscitation (CPR). E-CPR is the last rescue therapy when, despite high-quality conventional CPR, it is not possible to achieve the return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA). The probability of achieving ROSC and survival declines rapidly after ten minutes of resuscitation [1,2] and less than 1% of patients survive with a favorable neurological outcome after 35 minutes of conventional CPR . In such situations, OHCA is considered refractory, and E-CPR recently demonstrated to improve outcomes among patients with favorable prognostic factors (e.g., young age, witnessed cardiac arrest, early bystander CPR and short no-flow time, signs of life, shockable rhythm) [3–5].
In this issue of the Journal of Cardiothoracic and Vascular Anesthesia, Kruit and colleagues  report the results of a systematic review and meta-analysis investigating the effect of pre-hospital initiation of E-CPR on low-flow time (interval from CPR to ECMO initiation) and survival. A 2018 review identified that most evidence for pre-hospital E-CPR came from a small case series . In their systematic review, Kruit and colleagues  included three new observational studies for a total of four studies and 222 patients treated with pre-hospital E-CPR . Most patients come from a study conducted in a single EMS system in Paris , the first EMS system applying pre-hospital E-CPR since 2011.
Pre-hospital E-CPR is one of the two main strategies to provide E-CPR for patients with refractory OHCA (Figure 1). In this scenario, ECMO is established at the place of OHCA (e.g., home, street, workplace, or public place) and the patient is transported to the accepting cardiac arrest center once ECMO cannulation is completed. However, pre-hospital E-CPR is not commonly adopted. A “load and go” strategy where the patient is rapidly transported with ongoing CPR to an ECPR-capable center is far more widespread among systems offering E-CPR and was recently investigated in two randomized trials [3,4]. In this scenario, ECMO cannulation is performed after hospital arrival in the emergency department, catheterization laboratory, or intensive care unit. Another worth mentioning strategy, still not frequently applied, is the rendezvous approach : the non-ECMO ambulance rapidly transports the patient with ongoing CPR to a meeting point (e.g., a spoke emergency department acting as the cannulation site) halfway with the mobile E-CPR team. The patient is then transported to the hub ECMO center for post-resuscitation care.
Table 1Pros and cons of pre-hospital initiation of extracorporeal cardiopulmonary resuscitation.
Reduction of low-flow time
Avoidance of transport with ongoing CPR
Increase the catchment of eligible patients
Equity also in rural areas or areas far from E-CPR centers
Requirement of specialized equipment and skills not universally available in the pre-hospital setting
Cannulation in complex and less controlled environments
Difficulties in managing early complications
Delay of diagnosis and other treatments (e.g., coronary angiography, imaging, other mechanical circulatory devices)
Initiating E-CPR at the site of OHCA potentially reduces low-flow time by avoiding delays due to patient extraction and ambulance transport, common issues in metropolitan cities. In their meta-analysis of pre-hospital E-CPR, Kruit and colleagues reported a pooled mean low-flow time of 61 minutes (95% CI, 45–77) . Since shorter low-flow times are associated with better outcomes  and pre-hospital E-CPR pursues this goal precisely, one might expect a lower low-flow time. A careful reader will notice that the low-flow time reported by Kruit et al. in their meta-analysis is similar to the mean low-flow times for in-hospital E-CPR in the ARREST trial (59±28 minutes)  and in the Prague OHCA study (61 [IQR 55–70] minutes) . However, if we move from the setting of randomized trials to that of observational studies, mean low-flow times for in-hospital E-CPR were highly variable and tended to have high values . These observations highlight the difficulties in staying within the optimal window of 60 minutes of low-flow (golden hour for E-CPR) for most patients, even when initiating E-CPR in the pre-hospital setting. The Paris strategy significantly reduced the mean low-flow time, with similar cannulation time, success, and complication rates compared to in-hospital E-CPR .
Concerning survival after pre-hospital E-CPR, Kruit et al. calculated a pooled survival to hospital discharge of 23% (95% CI, 16–34%) in patients treated with pre-hospital E-CPR. This is a significant achievement considering the pooled low-flow time of 61 minutes. However, the absence of a comparator and the small number of studies and patients included prevent from drawing any firm conclusions on the effect of pre-hospital E-CPR on survival. Only one observational study in Paris, France compared pre-hospital E-CPR with in-hospital E-CPR . In this cohort of 525 E-CPR patients, pre-hospital cannulation was an independent predictor of higher survival and favorable neurological outcome (OR 2.9, 95% CI 1.5–5.9, p=0.002, and OR 2.9, 95% CI 1.3–6.4, p=0.008, respectively) . Aiming at the goal of “no-flow zero” with early CPR and defibrillation remains the cornerstone of OHCA: bystanders have an unquestionable benefit and are the primary drivers of survival and good neurological outcome. For example, low-cost, high-impact smartphone apps that alert citizen first responders to nearby OHCAs to provide early CPR and defibrillation should be first implemented in every country . Adding E-CPR to the chain of survival with hope for favorable neurological outcome is only possible for patients who benefit from bystander CPR.
It is clear that treating refractory OHCA patients with E-CPR poses unique logistical challenges in addition to clinical ones. The potential reduction in low-flow that pre-hospital E-CPR can offer and the improvement in survival are not only determined by initiating ECMO at the site of OHCA but also by EMS system organization, rapid identification of eligible patients, and early activation of the E-CPR team and ECMO implementation. In addition, many other unpredictable factors, well-known to pre-hospital emergency medicine clinicians, may affect the desired outcome. The clinical benefits of earlier treatment and shorter low-flow time must also be balanced with the substantial costs and resources needed, including specialized equipment and personnel. Furthermore, it is essential to consider that pre-hospital E-CPR cannulation is performed in a more complex and unpredictable environment.
On the other hand, in-hospital E-CPR is performed in a more controlled setting, with the immediate availability of advanced equipment, diagnostics, and other healthcare professionals, facilitating the procedure and the management of complications. However, it requires reaching the dedicated hospital ideally within 60 minutes, a goal that remains difficult to achieve. Although the decision to transport the patient must be taken as early as possible, it should not be made at the expense of CPR quality . Moreover, in-hospital E-CPR is not available everywhere (i.e., in rural areas), and pre-hospital E-CPR can be the only solution for some patients . In pre-hospital E-CPR, the time issue may shift to the post-cannulation phase as the patient may need to be transported to a significant distance, potentially delaying diagnosis and other treatments (e.g., coronary angiography, imaging, other mechanical circulatory devices) that with in-hospital E-CPR would be immediately available after cannulation.
Randomized studies comparing pre-hospital versus in-hospital E-CPR are currently lacking, as observed by Kruit et al. in their systematic review . The ON-SCENE trial (NCT04620070) is currently randomizing patients in The Netherlands to pre-hospital E-CPR provided through EMS helicopters versus conventional resuscitation. However, we will have to wait until 2026, the expected study completion date, to see the potential effect on survival. Long-term outcomes and quality of life after pre-hospital E-CPR are still unavailable and should be investigated in future studies. Until then, according to the available data, E-CPR should be anticipated and made available either way for eligible patients, adapting to existing local resources to limit low-flow time as much as possible.
In conclusion, there is very low certainty of evidence supporting the use of pre-hospital E-CPR. The work conducted by Kruit et al.  in this evolving field of resuscitation constitutes an important appraisal of the available evidence, helpful in informing the design of future studies and understanding current knowledge gaps. E-CPR is the last rescue therapy for patients with refractory OHCA: when applied, low-flow time should be minimized, but the best strategy remains to be demonstrated and may be dependent on factors specific to each system. Nowadays, pre-hospital E-CPR could be the most effective way, but it requires considerable resources and skills not universally available in the pre-hospital setting.
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To evaluate the available published evidence of the effects of extracorporeal cardiopulmonary resuscitation (ECPR) in the prehospital setting on clinical outcomes in patients with out-of-hospital cardiac arrest.