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. 2022 Aug 24;35(4):ivac219. doi: 10.1093/icvts/ivac219

Systematic review and meta-analysis comparing low-flow duration of extracorporeal and conventional cardiopulmonary resuscitation

Loes Mandigers 1,2,✉, Eric Boersma 3, Corstiaan A den Uil 4,5,6, Diederik Gommers 7, Jan Bělohlávek 8, Mirko Belliato 9, Roberto Lorusso 10, Dinis dos Reis Miranda 11
PMCID: PMC9491846  PMID: 36000900

Abstract

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OBJECTIVES

After cardiac arrest, a key factor determining survival outcomes is low-flow duration. Our aims were to determine the relation of survival and low-flow duration of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) and if these 2 therapies have different short-term survival curves in relation to low-flow duration.

METHODS

We searched Embase, Medline, Web of Science and Google Scholar from inception up to April 2021. A linear mixed-effect model was used to describe the course of survival over time, based on study-specific and time-specific aggregated survival data.

RESULTS

We included 42 observational studies reporting on 1689 ECPR and 375 751 CCPR procedures. Of the included studies, 25 included adults, 13 included children and 4 included both. In adults, survival curves decline rapidly over time (ECPR 37.2%, 29.8%, 23.8% and 19.1% versus CCPR-shockable 36.8%, 7.2%, 1.4% and 0.3% for 15, 30, 45 and 60 min low-flow, respectively). ECPR was associated with a statistically significant slower decline in survival than CCPR with initial shockable rhythms (CCPR-shockable). In children, survival curves decline rapidly over time (ECPR 43.6%, 41.7%, 39.8% and 38.0% versus CCPR-shockable 48.6%, 20.5%, 8.6% and 3.6% for 15, 30, 45 and 60 min low-flow, respectively). ECPR was associated with a statistically significant slower decline in survival than CCPR-shockable.

CONCLUSIONS

The short-term survival of ECPR and CCPR-shockable patients both decline rapidly over time, in adults as well as in children. This decline of short-term survival in relation to low-flow duration in ECPR was slower than in conventional cardiopulmonary resuscitation.

Trial registration

Prospero: CRD42020212480, 2 October 2020.

Keywords: Heart arrest, Cardiac arrest, Cardiopulmonary resuscitation, Extracorporeal cardiopulmonary resuscitation, Survival

Despite mounting research, cardiac arrest remains a major cause of death worldwide [1].

INTRODUCTION

Despite mounting research, cardiac arrest remains a major cause of death worldwide [1]. Although improvements have been seen in the conventional cardiopulmonary resuscitation (CCPR), in the education of laypersons to perform basic life support, and in the use of defibrillators or automated external defibrillators, survival outcomes after cardiac arrest remain poor. Previous studies have shown that various prognostic factors are associated with short-term survival, including age, initial cardiac rhythm, time to return of spontaneous circulation (ROSC), whether or not bystanders attempt basic life support, and how quickly this basic life support is provided [2–4]. Of these prognostic factors, time to ROSC has a major influence on this short-term survival and—unlike factors such as age—is also a factor over which we have some control [5].

One way of shortening the low-flow duration could be the use of extracorporeal cardiopulmonary resuscitation (ECPR). ECPR involves applying an extracorporeal membrane oxygenator during CPR and can be used in both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). Due to transportation times, the use of ECPR in OHCA patients can be more challenging, whilst most hospitals use maximum low-flow durations in order to be eligible for ECPR. Despite the possible advantages of the use of ECPR to shorten low-flow duration and improve outcomes, one should take into account that this therapy is expensive and could result in severe complications.

The low-flow duration is defined as the elapsed interval from resuscitation until one of 3 endpoints: ROSC, artificial return of circulation using ECPR or death. ECPR treatment is used to limit ischaemic damage and buy time to resolve the cause of cardiac arrest. In a randomized controlled trial, survival outcome of ECPR patients was much higher than in CCPR patients [6]. Two recent meta-analyses have shown the potential benefit on short-term survival of adding ECPR to CCPR [7, 8]. It is clear that the longer the low-flow state is present, the poorer the survival outcome will be [9–11]. The most recent meta-analysis showed that a shorter low-flow duration in ECPR is associated with improved survival [8]. Previously propensity-matched observational studies show different results ranging from improved outcomes for ECPR to no difference in outcomes for ECPR and CCPR [12–17].

Information regarding low-flow duration and survival will contribute to organize ECPR treatment as efficient as possible. Therefore, the aims of this systematic review and meta-analysis were therefore to determine (i) the relation of survival and low-flow duration of both ECPR and CCPR and (ii) if ECPR and CCPR have different survival curves in relation to low-flow duration. We intended to stratify these analyses for adults and children and for OHCA and IHCA.

MATERIALS AND METHODS

This systematic review and meta-analysis are performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [18] and it is listed in the PROSPERO register with registration number CRD42020212480. Study eligibility criteria, search study selection, data extraction and risk of bias assessment are described in detail in the Supplementary Material, Appendix S1. In short, a systematic search in Embase, Medline, Web of Science and Google Scholar was performed from inception up to April 2021. All studies including at least 20 OHCA or IHCA patients treated with ECPR or CCPR were included. Two researchers screened and included the studies and performed data extraction, including study characteristics, patient characteristics, clinical characteristics and outcomes.

Statistical analysis

The study characteristics, patient characteristics, clinical characteristics and outcomes were described for each study. The studies were grouped by adults, children or both. We report continuous variables using mean and standard deviation (SD) or median and interquartile ranges (IQR) where applicable. We report categorical variables using numbers and percentages.

As primary outcome, we studied the relation of short-term survival and low-flow duration. As secondary outcome, the short-term survival in relation to low-flow duration of ECPR and CCPR were compared. Outcome measures differed by study. Studies in which hospital survival was mentioned, this was used as the primary outcome parameter. For studies in which only neurologically intact survival was mentioned, or 30-day, 90-day or 1-year survival: all these outcome parameters were considered as ‘hospital survival’. Including all of these patients will result in a lower short-term survival rate than the actual survival rate and therefore this will be an underestimation of short-term survival. Actual numbers would be higher. If only intensive care unit survival was mentioned in the study, these studies were excluded. In case no individual data were available, we contacted the authors for the exact low-flow durations, followed by a reminder after 1 month if necessary. If we received no response or if the data were not available, we used the time intervals of low-flow duration.

In order to be able to analyse the data of the studies which reported individual data, we had to cluster the low-flow durations with a minimum of 5 events per group. For the studies of which only low-flow duration intervals were available, we calculated the average value of every time interval per study, as this was the best possible approximation for the value of each individual patient. Next, for the maximum values, mostly a value ‘higher than’ (>) a specific value was mentioned. We approximated this value by calculating the mean (SD) and determined low-flow duration belonging to the 87.5 percentile. If there was no mean value mentioned in the articles, we used the median (IQR).

Linear mixed effect (LME) models were used to describe the course of survival over time in relation to ECPR versus CCPR, while accounting for clustering of data within a study. The 2log probability of survival was modelled as a function of time, based on study- and time-specific aggregated survival data, which were weighed according to the inverse variance method. Results are presented as exponential functions. We analysed data of adults and children separately. In adults and in children, we combined shockable and non-shockable initial cardiac rhythm for ECPR patients due to the limited amount of data. For CCPR patients, shockable initial cardiac rhythm (CCPR-shockable) and non-shockable initial cardiac rhythm (CCPR-non-shockable) were analysed separately. We compared ECPR patients to CCPR-shockable patients as shockable rhythm is usually an inclusion criterion for ECPR. Also, ECPR patients are mostly selected based on patient criteria which increase the chances of favourable outcome, as CCPR-shockable patients are the patients with expected better outcomes than in CCPR-non-shockable patients. By selecting the CCPR-shockable patients, mostly patients with cardiac cause of arrest will be included. In case studies including CCPR patients in which initial cardiac rhythm was not classified, were excluded for the analysis.

RESULTS

Study selection

We identified 5117 studies with our search, after removing duplicates, there were 2461 studies remaining. After title and abstract screening, 193 studies were selected for full-text screening. Of those, 48 were excluded because the outcomes were not presented in time intervals, 34 were excluded because the primary endpoint could not be obtained, 9 were excluded because of multiple studies in the same cohort, 9 studies were excluded because these only included patients achieving ROSC and 51 were excluded for other reasons, as shown in Fig. 1. Finally, we included 42 studies (N = 417,133) [9, 11, 14, 19–57], of which 25 studies included only adult patients, 13 studies included only children and 4 studies included both.

Figure 1:

Figure 1:

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Flowchart of study selection using the PRISMA guidelines.

Characteristics

Table 1 shows the study characteristics and a more detailed description is shown in Supplementary Material, Table S100. Three of the adult studies included patients treated with ECPR or CCPR, 11 studies included only patients treated with ECPR and 10 included only patients treated with CCPR. In the studies in children, 1 study included patients treated with ECPR or CCPR, 5 studies included only patients treated with ECPR and 7 studies included only patients treated with CCPR. In the studies including both adults and children, 1 study included patients treated with ECPR or CCPR, 2 studies included only patients treated with ECPR and 1 study included only patients treated with CCPR.

Table 1:

Study characteristics

No Study Year Adults/Children/Both Study design Inclusion period Setting (single/multi-centre) Maximum follow-up duration ECPR/CCPR/both Patient number Follow-up duration included in analyses Mean low-flow duration (min)
Studies in adults
1 Adnet [9] 2017 Adults Descriptive 2011–2015 Multi 30 days CCPR 27 301 30 days 30.0 (10.0–50.0)
2 Bartos [51] 2020 Adults Case-control 2015–2019 Multi Hospital stay Both 1134 Hospital stay ECPR 60.0 ± 1.0
CCPR 35.0 ± 1.0
3 Chen [21] 2008 Adults Descriptive 1994–2005 Single 5 years ECPR 135 Hospital stay 52.8 ± 37.2
4 Chou [22] 2014 Adults Case-control 2006–2010 Single Hospital stay Both 66 Hospital stay ECPR 59.7 ± 34.1
CCPR 49.4 ± 34.6
5 Dumot [23] 2001 Adults Descriptive 1994–1995 Single Hospital stay CCPR 445 Hospital stay NR
6 Ferguson [24] 2008 Adults Descriptive 2001–2005 Single 6 months CCPR 256 Hospital stay NR
7 Fjolner [45] 2017 Adults Descriptive 2011–2015 Single Hospital stay ECPR 21 Hospital stay 121.0 (55.0–192.0)
8 Goldberger [25] 2012 Adults Descriptive 2000–2008 Multi Hospital stay CCPR 64 339 Hospital stay 17.0 (10.0–26.0)
9 Grunau [27] 2018 Adults Descriptive 2007–2011 Multi Hospital stay CCPR 5674 Hospital stay 13.0 (7.2–20.8)
10 Haneya [47] 2012 Adults Descriptive 2007–2012 Single Hospital stay ECPR 85 Hospital stay 51.0 ± 35.0
11 Kim [14] 2014 Adults Cohort 2006–2013 Single 3 months Both 499 3 months ECPR 62.0 (47.0–89.0)
CCPR 35 (21.0–50.0)
12 Mandigers [55] 2021 Adults Descriptive 2010–2020 Single Hospital stay ECPR 84 Hospital stay 51.0 (37.0–80.0)
13 Murakami [52] 2020 Adults Descriptive 2010–2015 Single 30 days ECPR 1630 30 days NR
14 Nagao [34] 2016 Adults Descriptive 2005–2012 Multi 30 days CCPR 28 2183 30 days NR
15 Otani [35] 2018 Adults Descriptive 2009–2017 Single Hospital stay ECPR 135 Hospital stay 47.0 (43.0–57.0)
16 Park [50] 2019 Adults Descriptive 2013–2016 Multi Hospital stay ECPR 689 Hospital stay NR
17 Pionkowski [36] 1983 Adults Descriptive 1978–1982 Single Hospital stay CCPR 565 Hospital stay NR
18 Pound [53] 2020 Adults Descriptive 2017–2018 Multi Hospital stay CCPR 152 Hospital stay 6.0 (2.0–18.0)
19 Reynolds [38] 2016 Adults Descriptive 2007–2010 Multi Hospital stay CCPR 11 368 Hospital stay 20.0 (12.0–27.3)
20 Rosenberg [39] 1993 Adults Descriptive 1988–1989 Multi Hospital stay CCPR 300 Hospital stay NR
21 Siao [57] 2020 Adults Descriptive 2012–2017 Single Hospital stay ECPR 112 Hospital stay 46.0 (35.0–57.0)
22 Valentin [48] 1995 Adults Descriptive 1989–1991 Single Hospital stay CCPR 253 Hospital stay 30.7 (SD/IQR not mentioned)
23 Wang [42] 2014 Adults Cohort 2007–2012 Single Hospital stay ECPR 230 Hospital stay OHCA 67.5 ± 30.6
IHCA 44.4 ± 24.7
24 Wengenmayer [11] 2017 Adults Cohort 2010–2016 Single Hospital stay ECPR 133 Hospital stay 59.6 ± 5.0
25 Yukawa [44] 2017 Adults Descriptive 2011–2015 Single Hospital stay ECPR 79 Hospital stay 45.0 (40.0–56.5)
Studies in children
26 Bembea [19] 2013 Children Descriptive 2000–2014 Multi Hospital stay ECPR 593 Hospital stay 48.0 (28.0–70.0)
27 Ganesan [46] 2018 Children descriptive 2012–2014 Single Hospital stay CCPR 137 Hospital stay 20.0 (SD/IQR not mentioned)
28 Goto [26] 2016 Children Descriptive 2005–2012 Multi 30 days CCPR 12 877 30 days NR
29 Innes [49] 1993 Children Descriptive 1990–1991 Single 1 year CCPR 41 30 days NR
30 Kalloghlian [29] 1998 Children Descriptive 1989–1992 Single Hospital stay CCPR 234 Hospital stay NR
31 Kramer [54] 2020 Children Descriptive 2005–2016 Single Hospital stay ECPR 72 Hospital stay 60.0 (42.0–80.0)
32 Lopez [31] 2004 Children Descriptive 1998–1999 Multi 1 year CCPR 283 1 year NR
33 Lopez [30] 2013 Children Descriptive 2007–2009 Multi Hospital stay CCPR 502 Hospital stay NR
34 Matos [32] 2013 Children Descriptive 2000–2009 Multi Hospital stay Both 3419 Hospital stay NR
35 Meert [56] 2019 Children Descriptive 2009–2015 Multi 1 year ECPR 147 1 year NR
36 Morris [33] 2004 Children Cohort 1995–2002 Single Hospital stay ECPR 64 Hospital stay 50.0 (SD/IQR not mentioned)
37 Rathore [37] 2016 Children Descriptive 2011–2012 Single 1 year CCPR 314 Hospital stay 10.0 (3.0–30.0)
38 Sivarajan [41] 2011 Children Descriptive 1990–2006 Single 2 year ECPR 37 Hospital stay 30.0 (15.0–50.0)
Studies in adults and children
39 Chen [20] 2016 Both Descriptive 2012 Single Hospital stay Both 382 Hospital stay 28.0 (10.0–50.0)
40 Hendrick [28] 1990 Both Cohort 1986–1988 Single 1–18 months CCPR 90 Hospital stay NR
41 Shinn [40] 2009 Both Descriptive 2004–2006 Single Hospital stay ECPR 50 Hospital stay 51.1 ± 27.8
42 Younger [43] 1999 Both Descriptive 1991–1998 Single Hospital stay ECPR 23 Hospital stay NR
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Study characteristics of the included papers.

CCPR: conventional cardiopulmonary resuscitation; ECPR: extracorporeal cardiopulmonary resuscitation; IHCA: in-hospital cardiac arrest; IQR: interquartile range; OHCA: out-of-hospital cardiac arrest; SD: standard deviation.

Patient and clinical characteristics are shown in Supplementary Material, Table SA. For the adult studies, 1470 patients treated with ECPR and 375 751 patients treated with CCPR were included. For the studies in children, 1140 patients treated with ECPR and 17 653 patients treated with CCPR were included. For the studies including both adults and children, 111 patients treated with ECPR and 436 patients treated with CCPR were included.

Quality assessment

All available studies had an observational design: therefore, the overall quality of evidence was low. With respect to this low quality of evidence, we used the Newcastle-Ottawa Scale (NOS) to distinguish of quality within the included studies (Supplementary Material, Table SB).

Outcomes

The short-term survival percentages we present are calculated using the following LME models. In adult ECPR patients (combining shockable and non-shockable initial cardiac rhythms): Hospital survival (%) = 2(5.5383–(0.02139*time)), time is being given in min of low-flow time. In adult CCPR-shockable patients: Hospital survival (%) = 2(7.5645–(0.1574*time)). Due to one highly influencing study, no LME model could be created for adult CCPR-non-shockable patients. In paediatric ECPR patients (combining shockable and non-shockable initial cardiac rhythms): Hospital survival (%) = 2(5.5139–(0.00442*time)). In paediatric CCPR-shockable patients: Hospital survival (%) = 2(6.8488–(0.08312*time)). In paediatric CCPR-non-shockable patients: Hospital survival (%) = 2(4.4677–(0.0598*time)). In order to compare the ECPR and CCPR-shockable patients, we first arbitrarily determined a difference of 5% survival as clinically relevant. Next, we tested if there is any statistical difference between the course of the LME of ECPR and CCPR-shockable patients.

In 39 of the 42 studies, short-term survival was available, the remaining 3 studies 3 months/1 year survival was included as short-term survival. The survival outcomes are shown in Table 2. In adults, short-term survival ranged from 9.3% to 46.4% in ECPR, and from 5.4% to 39.5% in CCPR. In children, short-term survival ranged from 34.4% to 40.6% in ECPR, and from 9.1% to 46.3% in CCPR. In the studies including both adults and children, short-term survival ranged from 19.4% to 36.0% in ECPR, and from 11.0% to 16.5% in CCPR. In Supplementary Material, Table S500, we summarized the outcomes stratified for OHCA and IHCA patients, for the studies in which this information was available.

Table 2:

Outcomes

No Study Short-term survival (hospital/30 day)
 Long-term survival (3 months/6 months/1 year)
 Survival with CPC score ≤2
ECPR CCPR ECPR CCPR ECPR CCPR
Studies in adults
1 Adnet 1482 (5.4) 1249 (4.5)
2 Bartos 52 (39.0) 148 (23.0) 52 (39.0) 52 (39.0) 148 (23.0)
3 Chen 46 (34.1) 43 (31.9) 41 (30.4)
4 Chou 15 (34.9) 5 (21.7)
5 Dumot 104 (23.0)
6 Ferguson 32 (13.0) 16 (6.0) 15 (5.9)
7 Fjolner 7 (33.3) 7 (33.3)
8 Goldberger 9912 (15.4) 7034 (10.9%, 1188 missings)
9 Grunau 690 (12.2) 292 (5.1%, 306 missings)
10 Haneya 29 (34.1) 27 (31.7)
11 Kim 9 (16.4) 86 (19.4) 8 (14.5) 44 (9.9) 8 (14.5) 36 (8.1)
12 Mandigers 24 (28.6)
13 Murakami 32 (37.6) 14 (16.5)
14 Nagao 21,658 (7.7) 9669 (3.4)
15 Otani 34 (25.0) 22 (16.3)
16 Park 13 (9.3) 7 (5.0)
17 Pionkowski 262 (46.4)
18 Pound 60 (39.5) 43 (28.3)
19 Reynolds 1232 (10.8) 905 (8.0)
20 Rosenberg 82 (23.5)
21 Siao 45 (40.2) 41 (36.6) 34 (30.4)
22 Valentin 50 (19.8) 44 (17.4)
23 Wang 74 (32.2) 58 (25.2)
24 Wengenmayer 19 (14.3)
25 Yukawa 17 (21.5) 11 (13.9)
Studies in children
26 Bembea 241 (40.6) 108 (18.2%, 125 missings)
27 Ganesan 27 (19.7) 21 (15.3)
28 Goto 1167 (9.1) 325 (2.5)
29 Innes 19 (46.3) 16 (39)
30 Kalloghlian 66 (28.2)
31 Kramer 26 (36.1) 22 (30.6) 19 (26.4)
32 Lopez 98 (34.6) 94 (33.2)
33 Lopez 197 (39.2) 104 (88.9)
34 Matos 78 (34.4) 876 (27.4)
35 Meert 32 (22.1) 39 (30.5)
36 Morris 23 (35.9) 26 (35.6) 5 (50.0%, 3 missings)
37 Rathore 44 (14.0) 35 (11.1) 27 (8.6)
38 Sivarajan 14 (37.8) 12 (32.4) 4 (10.8)
Studies in adults and children
39 Chen 7 (19.4) 38 (11.0)
40 Hendrick 15 (16.5)
41 Shinn 16 (32.0)
42 Younger 9 (36.0)
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Survival outcome and neurologic favourable outcome for all included studies. Values are presented as number (%).

CCPR: conventional cardiopulmonary resuscitation; CPC: cerebral performance category; ECPR: extracorporeal cardiopulmonary resuscitation.

Primary and secondary outcome

In adults, both survival curves of ECPR patients and CCPR-shockable patients showed a decline in survival with increase of low-flow duration. When comparing the survival curves of adults, the decline in survival outcome for increasing low-flow duration was significantly slower (P < 0.01) in patients treated with ECPR than in CCPR-shockable patients, as shown in Fig. 2. Short-term survival at 15 min low-flow duration was 37.2% in ECPR and 36.8% in CCPR-shockable. In ECPR, short-term survival declined, from 34.5% at 20 min to 29.8% at 30 min, 23.8% at 45 min and 19.1% at 60 min. In CCPR-shockable, short-term survival declined, from 21.4% at 20 min to 7.2% at 30 min, 1.4% at 45 min and 0.3% at 60 min. The difference in survival outcome was at least 5% higher in ECPR than in CCPR-shockable starting from 16.5 min. This difference increased to 22.6% at 30 min and 18.8% at 60 min low-flow duration. Unfortunately, we were unable to estimate a linear mixed model for CCPR-non-shockable patients due to major influence of one study.

Figure 2:

Figure 2:

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Relation between low-flow duration in minutes and hospital survival in percentage in adult patients treated with extracorporeal cardiopulmonary resuscitation (ECPR, red diagonal line: Hospital survival (%) = 2(5.5383–(0.02139*time (in min)))), conventional cardiopulmonary resuscitation (CCPR) due to shockable initial cardiac rhythms (blue parabole: Hospital survival (%) = 2(7.5645–(0.1574*time (in min)))), CCPR due to non-shockable initial cardiac rhythms (yellow dots no line). Calculated using LME models shown above. Due to one highly influencing study, no LME model could be created for CCPR patients with non-shockable cardia rhythm. LME: linear mixed effect (A color version of this figure appears in the online version of this article).

In children, all of the survival curves of ECPR patients, CCPR-shockable patients, and CCPR-non-shockable patients showed a decline in survival with increase of low-flow duration. When comparing the survival curves of children, the decline in survival outcomes for increasing low-flow duration was significantly slower (P < 0.01) in patients treated with ECPR than in CCPR-shockable patients, as shown in Fig. 3. In ECPR, short-term survival declined from 43.6% at 15 min to 41.7% at 30 min, 39.8% at 45 min and 38.0% at 60 min. In CCPR-shockable patients, short-term survival declined from 48.6% at 15 min to 20.5% at 30 min, 8.6% at 45 min and 3.6% at 60 min. In CCPR-non-shockable patients, short-term survival declined from 11.9% at 15 min to 6.4% at 30 min, 3.4% at 45 min and 1.8% at 60 min. The short-term survival was at least 5% higher in ECPR than in CCPR-shockable patients starting from 19.2 min. This difference increased to 21.2% at 30 min, and 34.4% at 60 min low-flow duration.

Figure 3:

Figure 3:

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Relation between low-flow duration in minutes and hospital term survival in percentage in children treated with extracorporeal cardiopulmonary resuscitation (ECPR, red upper diagonal line: Hospital survival (%) = 2(5.5139–(0.00442*time (min)))), conventional cardiopulmonary resuscitation (CCPR) due to shockable initial cardiac rhythms (blue, parabole line: Hospital survival (%) = 2(6.8488–(0.08312*time (min)))), CCPR due to non-shockable initial cardiac rhythms (yellow lower diagonal line: Hospital survival (%) = 2(4.4677–(0.0598*time (min)))). Calculated using LME models shown above. LME: linear mixed effect (A color version of this figure appears in the online version of this article).

DISCUSSION

The results of our systematic review and meta-analysis show a decline in survival with increase of low-flow duration in both ECPR and CCPR patients. This decline in short-term survival for increasing low-flow duration is significantly slower in patients treated with ECPR than in CCPR-shockable patients, for both adults as children.

The fact that we found a slower decline in survival for increasing low-flow duration in favour of ECPR in both adults and children is in line with the findings of a previous study by Bartos et al. [51]. They recently compared survival outcomes of adults treated with ECPR and CCPR for increasing low-flow durations and found the decline in neurologically favourable survival to be slower in ECPR than in CCPR [51]. Although this study was performed in a smaller group of patients and used a slightly different outcome (neurologically favourable survival rather than just survival), the slower decline in survival for ECPR was similar to that seen in our results. This difference in the decline of short-term survival implies that the sooner ECPR is performed, the greater the chances of a favourable outcome.

The finding in our study that survival outcomes in ECPR are higher than those of CCPR is generally in line with the results of previous studies [7, 8]. In the first randomized controlled trial comparing ECPR to CCPR, Yannopoulos et al. [6] found a short-term survival rate of 43% in ECPR patients and 7% in CCPR patients. Previous systematic reviews comparing patients treated with ECPR and patients treated with CCPR have also shown higher survival outcomes [7, 8] and better neurological outcomes [8] in favour of ECPR. While 2 other recent systematic reviews did not observe this beneficial result for ECPR in OHCA patients, they did observe such a benefit in IHCA patients [58, 59]. Unfortunately, due to a lack of data, we were not able to analyse the outcomes for OHCA and IHCA separately. However, as indicated by Holmberg et al. [59], OHCA patients most likely experience longer low-flow durations than IHCA patients. The outcome difference of OHCA and IHCA is most probably caused by the difference in low-flow duration, the cause of the arrest and the primary rhythm.

With this study, we emphasize the importance of limiting the low-flow duration in both ECPR and CCPR patients. However, in most of the ECPR cases, low-flow durations shorter than 30 min are not always feasible. Especially in OHCA patients, the time until arrival to the hospital varies worldwide between 30 and 60 min [60–62]. Based on our results, we would suggest start preparing for ECPR—retrieve vascular access without dilatation—could be started before cannulation. Definitive cannulation could be started at 20 min low-flow duration. Worldwide, there are limited centres providing ECPR in the field [62], all others can only start ECPR after hospital arrival. Therefore, exploring the means for rapid transportation to the hospital or the ability to perform ECPR in the field is important in an attempt to decrease the low-flow duration. Several studies are recruiting patients or extending their study to research ECPR in the pre-hospital setting [6, 63, 64]. However, the possibilities of these special programmes, are not available globally.

Limitations

This study has some limitations. First, all studies that we included are influenced by confounding by indication. There is still no worldwide consensus regarding which patients are eligible for ECPR. Second, because of the lack of individual patient data we were not able to analyse OHCA and IHCA patients separately. When we stratified the data for ECPR and CCPR in time intervals and tried to stratify for OHCA and IHCA, the amount of data per cell was too limited to analyse. Due to the different causes of cardiac arrest in these 2 groups and the expected difference in the delay before starting CPR, this factor will probably influence the prognosis. Third, a large limitation is the heterogeneity of the study. Despite attempts of reducing this heterogeneity (especially follow-up duration and survival versus neurological favourable outcome), these data were also too limited to analyse. We included a table in the Supplementary Material (Table SE) mentioning the included data. By combining survival outcomes with favourable neurological outcomes in cases where raw survival outcomes were not given, some of the used data will be an underestimation of the survival outcomes. We included these outcomes as short-term survival in order to avoid overestimating. Fourth, all of the available studies are observational studies which hampers strong recommendations based on this study. Fifth, there might be differences in: willingness to start CPR by bystanders, use of automatic external defibrillators and transport times to the nearest hospital, which could not be taken into account. Finally, since we could not include all of the individual patient data, we had to determine average low-flow durations in order to pool the survival data. To overcome such a limitation in future meta-analysis—for example including the randomized controlled trials comparing ECPR and CCPR that are currently being conducted—these data should be pooled based on individual low-flow durations. This will allow for a more accurate comparison between the 2 groups.

CONCLUSION

The short-term survival of ECPR and CCPR-shockable patients both decline rapidly over time, in adults as well as in children. This decline of short-term survival in relation to low-flow duration in ECPR was lower than in CCPR.

SUPPLEMENTARY MATERIAL

Supplementary material is available at ICVTS online.

Supplementary Material

ivac219_Supplementary_Data
Click here for additional data file. (534.5KB, doc)

ACKNOWLEDGEMENTS

The authors want to thank Dr W. M. Bramer for his help with the systematic search.

Conflict of interest: Dinis dos Reis Miranda declares having received speaker fees from Xenios GmbH and HillRom GmbH. Diederik Gommers is a member of the medical advisory board of Xenios GmbH and received travel expenses and speaker fees from Xenios and Maquet GmbH. Roberto Lorusso is consultant for Medtronic and Livanova, and member of the medical advisory board of Eurosets srl (Medolla, Italy). Mirko Belliato is a member of the medical advisory board of Eurosets srl (Medolla, Italy) and congress speaker for Hamilton Medical (Bonaduz, Swiss).

Contributor Information

Loes Mandigers, Department of Adult Intensive Care, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Cardiology, Maasstad Hospital, Rotterdam, Netherlands.

Eric Boersma, Department of Cardiology, Erasmus University Medical Center, Rotterdam, Netherlands.

Corstiaan A den Uil, Department of Adult Intensive Care, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Cardiology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Intensive Care, Maasstad Hospital, Rotterdam, Netherlands.

Diederik Gommers, Department of Adult Intensive Care, Erasmus University Medical Center, Rotterdam, Netherlands.

Jan Bělohlávek, Department of Cardiovascular Medicine, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.

Mirko Belliato, UOC Anestesia e Rianimazione 2 Cardiopolmonare, Fondazione IRCC Policlinico San Matteo, Pavia, Italy.

Roberto Lorusso, Cardio-Thoracic Surgery Department, Heart & Vascular Centre, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, Netherlands.

Dinis dos Reis Miranda, Department of Adult Intensive Care, Erasmus University Medical Center, Rotterdam, Netherlands.

Data Availability Statement

The data underlying this article are available in the article and in its online supplementary material.

Author contributions

Loes Mandigers: Conceptualization; Data curation; Formal analysis; Methodology; Writing—original draft. Eric Boersma: Conceptualization; Data curation; Formal analysis; Methodology; Software; Supervision; Writing—review & editing. Corstiaan A. den Uil: Conceptualization; Supervision; Writing—review & editing. Diederik Gommers: Conceptualization; Writing—review & editing. Jan Bělohlávek: Conceptualization; Writing—review & editing. Mirko Belliato: Conceptualization; Writing—review & editing. Roberto Lorusso: Conceptualization; Writing—review & editing. Dinis dos Reis Miranda: Conceptualization; Data curation; Methodology; Supervision; Validation; Writing—review & editing.

Reviewer information

Interactive CardioVascular and Thoracic Surgery thanks Carlos A. Mestres and the other anonymous reviewer(s) for their contribution to the peer review process of this article.

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Data Availability Statement

The data underlying this article are available in the article and in its online supplementary material.

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