Our primary goal was to provide a comprehensive overview of current literature pertaining to neurological outcome after ECPR for in-hospital cardiac arrest. In post-discharge survivors, we found a high proportion of patients with a CPC 1-2 (84% [95% CI: 80-88%]), which is lower than described for 1-year survivors CCPR (92% [95% PI: 82 – 97%] ). Post-discharge survival was higher than reported for the general IHCA populations (30% [95% CI: 28-33%] versus 17% [95% PI: 13 –23%] [2,36]). We found little heterogeneity in outcome between studies.
Although neurological outcome is good, it remains inconclusive whether neurological outcome of patients receiving ECPR is better than patients receiving CCPR. We did find a lower percentage of “good” neurological outcome (CPC1-2) than in a systematic review in a conventional CPR population . However, in this review CPC score was a secondary outcome. In this review the proportion outcome assessment was also specifically set for one year, rather than after hospital discharge. A systematic review aimed at comparing ECPR and CCPR suggests that the neurological outcome is better in IHCA patients treated with ECPR compared to CCPR . Due to the observational nature of the studies included in these reviews, the selection of patients for ECPR could still lead to better outcomes for this group. For literature pertaining to OHCA the same caveats apply [38,39].
Comparing this study to the literature suggests that survival of IHCA patients undergoing ECPR is higher than IHCA populations who receive conventional CPR (chest compressions) [1,2]. Our estimate of survival is also comparable the reported survival rate of adult ECPR patients by the ELSO registry . This high survival might be explained by the selection of patients with a high chance of good outcome. The American Heart Association guidelines state that ECPR should be considered in patients for whom the suspected aetiology of the cardiac arrest is potentially reversible during a limited period of mechanical cardiorespiratory support . In contrast, the European Resuscitation Council simply declares that the technique is a potential rescue therapy in patients where standard advanced life support (ALS) measures are not successful . In practice, however, a much broader range of contra-indications are being used: this study found that the primary reported contra-indications were CPR duration, age, severe comorbidities such as terminal cancer or pre-existing neurological impairments, and uncontrolled bleeding. These contra-indications are known to impact prognosis. Excluding these patients from ECPR effectively results in a higher survival compared to patients receiving conventional CCPR. Especially the age criteria are quite stringent, and therefore likely affect the apparent survival , given the average age of the CPR population . Moreover, the finding that we found substantially less heterogeneity in survival rates between studies than a systematic review of the CCPR literature [1,2] also supports the hypothesis that this is a selected population. Nevertheless, part of the difference might be explained by the effect of ECPR versus CCPR on outcome [45–47].
On the other hand, ECPR is only indicated in patients with refractory cardiac arrest. Therefore, patients eligible for ECPR have, by indication, a worse prognosis than patients with conventional CPR as a portion of these patients ROSC after a short resuscitation period . As a result, ECPR patients might not be the patient population with the most favourable outcome.
Evidence in the literature suggests that a longer time to ECMO time is associated with lower benefit of ECPR [48–51]. Bartos et al. suggest the association between time to ECMO and survival is explained by the metabolic derangements, which develop during prolonged low-flow time, leading to a worse outcome . In our meta-analysis, this association between time to ECMO and survival is not found. However, most of the studies included in our meta-analysis do find a relationship between time to ECMO and survival, when this was investigated [18,22–27,34]. Possibly, our results can be explained due to an aggregation effect: our results imply that –because the variation in outcome between studies was small- differences in mean calculated time to ECMO do not explain differences in mean survival between studies. Additionally, our results might be explained by the long time to ECMO in the included studies (>30 minutes). Given that the success rate of CPR is very low when the duration is longer than 30 minutes [53,54], it might be more relevant to assess the effect of time to ECMO in when the time to ECMO is shorter. Since the effect of timing of ECPR on outcome impacts implementation, more high-quality evidence is needed.
Certain limitations should be taken into account. First, the time of CPC assessment was not the same for all studies. Most studies only scored CPC at the moment of discharge. This was not clearly defined in all studies. Some studies mentioned CPC scores at 6 months, others report a CPC score at discharge. We did show in a sensitivity analysis with the studies that reported data for the same follow-up moment that the estimates were very similar to the main analysis. However, a standardized and comprehensive assessment of neurologic and functional outcomes in cardiac arrest research is needed . In spite of these differences, we encountered homogenous results, which suggests that the time of outcome assessment did not significantly influence the results: the neurological outcome and survival seem to remain constant at different follow-up times. Second, the included studies had two main shortcomings: they were relatively small (the largest study included 200 patients), and often reported their data non-standardized and non-structured, which complicated the process of data extraction. Remarkably, we observed little heterogeneity between these small studies, which enabled us to perform a fixed-effects meta-analysis. Finally, we were not able to do an individual patient data meta-analysis. Since heterogeneity between studies was found, the effect of prognostic factors on outcome in these patients could not be explored effectively. An individual patient data meta-analysis would enable this , and could be of interest for future research.
By showing that treating a selected group of IHCA patients with ECPR can result in a high proportion of good neurological outcome, this study illustrates what next step the field should take. When centers become more experienced, the indications of ECPR will shift towards a less selected, but probably also more fragile patient population: older patients with more comorbidities might be considered eligible for ECPR in the near future. Nevertheless, we should focus on treating these patients while maintaining such a high proportion of favourable neurological outcome.