This study presents data of 1644 patients with OHCA, of which 69.4% had initial shockable rhythm and 14.1% had favorable neurological outcome at hospital discharge. The proportion of favorable neurological outcome was 16.7%, 9.2%, and 3.9% in patients with shockable rhythm, PEA, and asystole, respectively. The survival rate at hospital discharge was 32.0%, 18.5%, and 10.8% for patients with shockable rhythm, PEA, and asystole, respectively.

This study has several strengths. First, to the best of our knowledge, this study includes the largest cohort of patients with OHCA who received ECPR. Although several large cohort studies of (> 200) patients with OHCA who received ECPR have been reported in France [4], four other European countries [3], Korea [5], and Japan [6, 7, 9], this study included 1.5 times as much participants as the previous study with the largest number (916) of patients [6] and about half the number of patients in a recently published systematic review of ECPR for OHCA [26]. Second, unlike one previous study that included only patients with shockable rhythm [6], this study included patients with all types of cardiac rhythm. Third, this study included four institutions where more than 100 ECPRs were performed. Hence, the data used in this study can be considered a continuous dataset from institutions with low and high volumes of ECPR cases. Finally, this study described complications that were not considered in previous large studies [3,4,5,6,7, 9].

In previous studies that used detailed clinical data of more than 100 patients with OHCA who received ECPR, the proportion of favorable neurological outcome at discharge was 6–39% [3,4,5,6, 8, 9, 12,13,14, 17, 27, 28]. This study included different types of patients, and favorable neurological outcome was observed in 16.7% and 9.2% of patients who had shockable rhythm and PEA, respectively. In this study, the rate of witnessed cardiac arrest was approximately 88%, and bystander CPR was performed in 66% of patients. Further, the median estimated low flow time was 55 min in patients with PEA. The fact that the scatterplot curves of favorable neurological outcome and survival rate are different in terms of estimated low flow time between patients with PEA (i.e., low proportion of favorable neurological outcome despite relatively high survival rate over a short estimated low flow time) and patients with PEA strongly suggests heterogeneity. It is important to carefully determine suitable candidates for ECPR in initial PEA patients. In patients with initial asystole, ECPR may also be considered because, in select populations, the survival rate was greater than 10%.

Age is strongly associated with poor outcomes over time, and it is an independent prognostic factor, as shown with the large dataset used in this study. In previous studies, it was reported that the proportion of favorable neurological outcome in patients over 75 years of age is 1.7–2.9% [6, 7]. It may be necessary to determine cutoffs according to institution, region, and other factors. As with age, the outcomes of estimated low flow time worsened with time. Optimal limited low-flow time, defined as time from CPR initiation to ECPR, was reported by Otani et al. to be 58 min [29], and it was reported in several other studies to be within 60 min [3, 8, 27]. It is difficult to determine optimal limited low-flow time; therefore, it is important to minimize time to ECMO.

Regarding complications associated with ECPR, the most common complication was bleeding, with the rates of cannulation site bleeding and other types of hemorrhage at 16.4% and 8.5%, respectively, but it was reported to be 8–70% in previous studies [1]. Thirty percent of ECPRs were performed in relatively high-volume ECPR centers. This may be because the proportion of obese patients in Japan is lower than those in Western countries [20] and because of the high availability of skilled emergency physicians and acute care surgeons in the emergency departments of high-volume institutions [20]. Since ECPR-related complications are associated with poor outcome [30], it is necessary to shorten the time to ECMO and to initiate ECPR without complications. Training in cannulation technique may be considered in future training systems at high-volume ECPR centers to prevent and control complications.

Broad application of ECPR to patients with OHCA was observed in this study. This seems to be fundamentally associated with the national health insurance system in Japan [31]. Since medical bills are mainly paid by the Japanese government, physicians in charge do not pay attention to unpaid medical bills during ECPR initiation [32]. Moreover, in Japan, trained emergency physicians initiate ECPR with no involvement from cardiovascular surgeons; in contrast, in the USA, cardiovascular surgeons are usually involved throughout the entire ECMO process. Although a recently reported cost-effectiveness study on ECPR for patients with OHCA concluded that ECPR is a robust and economically acceptable resuscitative strategy after considering all parameters [33], it is difficult to establish uniform standard inclusion criteria. It may be possible to expand the indications for ECPR, but any expansion must be balanced by considering factors such as cost, complications, religious views, and local area-specific conditions. The large cohort dataset used in this study contains details of ICU management, CT data, cost, and socioeconomic status; therefore, a statistically confirmed study will provide robust conclusions and further hypotheses on ECPR.

Limitations

This study has several limitations. First, this was a retrospective study with variation of inclusion criteria in each participating institution; therefore, we reported the inclusion and exclusion criteria of all 36 SAVE-J II hospitals in another paper [20]. Second, there was no control group (i.e., a patient group that did not receive ECPR). Third, data on long-term outcome was not obtained. Fourth, confounders of time course, such as number of ROSC and total ROSC time until ECMO establishment, were not obtained from this dataset. Due to lack of various dataset, estimated low flow time would be different actual low flow time. Fifth, complications were a composite outcome, and specific complications were not assessed.

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