Extra-Corporeal Membrane Oxygenation (ECMO) for Postcardiotomy Cardiogenic Shock (PCCS) in Asian Patients: A Systematic Review and Meta-Analysis

doi:10.21203/rs.3.rs-501409/v1

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Extra-Corporeal Membrane Oxygenation (ECMO) for Postcardiotomy Cardiogenic Shock (PCCS) in Asian Patients: A Systematic Review and Meta-Analysis

https://doi.org/10.21203/rs.3.rs-501409/v1

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Background Extra-corporeal membrane oxygenation (ECMO) is an important extracorporeal life support system to treat patients with postcardiotomy cardiogenic shock (PCCS). But its effectiveness and safety are still inconclusive. Existing systematic reviews and meta-analysis have heterogeneity challenges such as the inclusion of different races in the same study.

Objective The impact of ECMO treatment on the survival rate of Asian adult patients with PCCS was evaluated by searching the literature and using the method of systematic review and meta-analysis.

Study Design and Methods PubMed, Web of Science, Cochrane Library, EMBASE, CNKI, WANFANG MED ONLINE, SinoMed were searched to find relevant research on the use of ECMO on PCCS patients in Asia. Outcomes included survival rate to hospital discharge, long-term survival rate, complications.

Results A total of 32 articles were selected, including observational studies and one RCT, involving China and Japan covering 4,278 PCCS patients. The pooled rate of survival to hospital discharge was 43.0% (95% CI 38% ~47%, I² = 87%), the pooled 1-year, 2-year, and 3-year survival rate were 34% (95% CI 26% ~ 42%, I² = 85%), 29% (95% CI 18% ~39%, I² = 93%), 25% (95%CI 16% ~35%, I²=93%). The pooled rate of bleeding, neurologic complications, rethoracotomy, leg ischemia, renal failure, renal replacement therapy, and infection were 18% (95% CI 13% ~24%, I²=91%), 13% (95% CI 9% ~17%, I² = 90.0%), 36% (95% CI 27% ~46%, I² = 97.0%), 11% (95% CI 9% ~13%, I² = 55%), 40% (95% CI 27% ~54%, I² = 90%), 45% (95% CI 35% ~ 56%, I² = 98%), 26% (95%CI (20%~31%, I²=95%).

Conclusion ECMO can provide survival benefits for Asian adult patients with PCCS. However, attention should be paid to reducing the incidence of complications, especially renal failure. More high-quality clinical studies are needed to confirm the survival benefit of ECMO.

Critical Care & Emergency Medicine

Asian

complication

extra-corporeal membrane oxygenation (ECMO)

postcardiotomy cardiogenic shock(PCCS)

survival outcome

Postcardiotomy cardiogenic shock (PCCS) is a severe complication after cardiac surgery. Intra-aortic balloon pump (IABP) and inotropic drugs are conventional treatment for these patients, but some patients still experience low cardiac function and insufficient cardiac output with the above supports. For these patients, effective mechanical circulation support (MCS) measures must be taken to prevent death. Extra-corporeal membrane oxygenation (ECMO) is an important mechanical circulation life support system to treat patients who do not respond well to high-dose vasoactive drugs and IABP. In recent years, studies have shown that about 1% of patients need ECMO due to cardiogenic shock after cardiac surgery ^[1–3]. Hu RTC et al ^[3] retrospectively analyzed adults treated with veno-arterial ECMO (VA-ECMO) for PCCS between 2001 and 2016 in Australia, they found that VA-ECMO improved survival rate, but morbidity was also increased. Lehmann S et al. ^[4] evaluated the clinical outcomes, 30 day and long-term follow-up in patients undergoing ECMO for refractory PCCS (n = 1040) and concluded that ECMO is an acceptable option for patients with PCCS and is justified by good long-term outcomes of hospital survivors.

Researchers also conducted systematic reviews and meta-analyses to evaluate the efficacy of ECMO for PCCS patients. However, their conclusions are inconsistence.

Khorsandi M et al. ^[5] including 24 retrospective cohort studies, concluded that VA-ECMO could provide survival benefits for patients with refractory PCCS. Harahwa TE et al. ^[6] found that the ECMO could improve the survival rate of PCCS patients for whom positive inotropic therapy was ineffective. This systematic review also found that without ECMO support, the death risk of patients would be increased. On the contrary, a systematic review by Wang L et al. ^[7] found that neither the short-term nor mid-term survival rates of PCCS patients treated with ECMO improved, accompanied with increased complications. In addition, we found these systematic reviews and meta-analyses were faced with heterogeneity challenges, for example, they pooled patients of different races together. We present hereby a systematic review and meta-analysis that attempt to evaluate the efficacy of ECMO for Asian PCCS patients.

The impact of ECMO treatment on survival rate of Asian adult patients with PCCS was systematically reviewed, and the meta-analysis was used when data are available.

3.1 Criteria for considering studies for this review

3.1.1 Types of participants: Asian adult patients with PCCS.

3.1.2 Types of interventions: treatment with ECMO.

3.1.3 Types of studies: retrospective studies, prospective study, randomized controlled trial (RCT).

3.1.4 Types of outcome measures

3.1.4.1 Primary outcomes: survival rate to hospital discharge.

3.1.4.2 Secondary outcomes: long-term survival rate (1-year, 2-year, 3-year survival rate), complications.

3.1.5 Exclusion criteria: literatures with less than 10 patients, studies only including patients after weaning, short report, ECMO used for bridging heart transplantation.

3.2 Search methods for identification of studies

PubMed, Web of Science, Cochrane Library, EMBASE, CNKI, WANFANG MED ONLINE, SinoMed were searched for articles published from inception to March 31, 2021, using the following search terms: “postoperative cardiogenic shock”, “post-operative cardiogenic shock”, “cardiogenic shock after surgery”, “PCCS”, “postcardiotomy cardiogenic shock”, “post-cardiotomy cardiogenic shock”, “Extracorporeal membrane oxygenation”, and “ECMO”. Specific search strategies are shown in Table 1.

Table 1

Search Strategies for ECMO Treatment on PCCS
Database	Search strategies
PubMed	((postoperative cardiogenic shock[Title/Abstract]) OR (post-operative cardiogenic shock[Title/Abstract]) OR (cardiogenic shock after surgery [Title/Abstract]) OR (PCCS[Title/Abstract]) OR (postcardiotomy cardiogenic shock[Title/Abstract]) OR (post-cardiotomy cardiogenic shock[Title/Abstract])) AND ((Extracorporeal membrane oxygenation[Title/Abstract]) OR (ECMO[Title/Abstract])) Filters applied: Adult: 19 + years
Web of Science	#1 AB = ECMO #2 AB = Extracorporeal Membrane Oxygenation #3 AB = post-cardiotomy cardiogenic shock #4 AB = postcardiotomy cardiogenic shock #5 AB = PCCS #6 AB = postoperative cardiogenic shock #7 AB = post-operative cardiogenic shock #8 AB = cardiogenic shock after surgery #9 #2 OR #1 #10 #8 OR #7 OR #6 OR #5 OR #4 OR #3 #11 #10 AND #9
Cochrane Library	#1 ECMO #2 Extracorporeal Membrane Oxygenation #3 post-cardiotomy cardiogenic shock #4 postcardiotomy cardiogenic shock #5 PCCS #6 postoperative cardiogenic shock #7 post-operative cardiogenic shock #8 cardiogenic shock after surgery #9 #2 OR #1 #10 #8 OR #7 OR #6 OR #5 OR #4 OR #3 #11 #10 AND #9
EMBASE	#1 'postoperative cardiogenic shock':ab,ti OR 'post-operative cardiogenic shock':ab,ti OR 'cardiogenic shock after surgery':ab,ti OR pccs:ab,ti OR 'postcardiotomy cardiogenic shock':ab,ti OR 'post-cardiotomy cardiogenic shock':ab,ti #2 'ecmo':ab,ti OR 'extracorporeal membrane oxygenation':ab,ti #3 #1 AND #2
CNKI	(((Abstract = postoperative cardiogenic shock or abstract_en = Chinese and English expansion (postoperative cardiogenic shock)) or (Abstract = postoperative cardiogenic shock or abstract_en = Chinese and English expansion (postoperative cardiogenic shock) )) And ((Abstract = Extracorporeal Membrane Oxygenation or abstract_en = Chinese and English expansion (Extracorporeal Membrane Oxygenation)) or (Abstract = Chinese and English expansion (ECMO) or abstract_en = ECMO))) (exact match), album navigation : All; Database: Literature cross-database search Search method: cross-database search Database: Literature
WANFANG MED ONLINE	((Abstract = Postoperative Cardiogenic Shock OR Abstract = Postoperative Cardiogenic Shock) AND (Abstract = ECMO OR Abstract = Extracorporeal Membrane Oxygenation))
SinoMed	("Postoperative Cardiogenic Shock"[Abstract:Smart] OR "Postoperative Cardiogenic Shock"[Abstract:Smart]) AND ("ECMO"[Abstract:Smart] OR "Extracorporeal Membrane Oxygenation"[Abstract: intelligent])

3.3 Selection of Studies and Data Extraction

Two researchers (LD, YT) independently carried out literature retrieve, screening, data extraction and quality evaluation. If there is a disagreement, it is resolved through discussion. The data extraction includes the baseline data of the patients included in the study, the number of IABP assistance, the type and incidence of complications.

3.4 Quality Assessment

The modified Newcastle-Ottawa scale was used to evaluate the quality of observational studies, ^[7] the Modified Jadad’s Scores Scale was used to evaluate the quality of RCT ^[8].

3.5 Statistical Analyses

Data analysis was performed using R version 4.0.3 software (the R Foundation) with the package of “meta” ^[9]. The results were expressed as pooled proportions (%) with 95% confidence interval (95% CI). Statistical heterogeneity was evaluated using the I² test (I² ༞50% was seen a high degree of statistically significant heterogeneity). Random-effect models were used because these are mainly observational studies. Publication bias was evaluated using the Egger test. Sensitivity analysis was performed to examine the stability of the results. A p value ༜0.05 was considered to be statistically significant.

4.1 Search Results and Study Characteristics

Through literature retrieval using the strategy we reported above, six-hundred and twenty-five records were found. After screening and evaluation, thirty-two articles were finally included for systematic review and meta-analysis ^[10–41]. The literature retrieval and screening process is shown in Fig. 1.

The included literature includes 2 studies from Japan ^{[12, 35]}, and the rest are from China. The publication date is between 2002 and 2020, including 29 retrospective studies, 2 prospective studies ^{[22, 23]}, and 1 RCT ^[19]. A total of 4278 PCCS patients were included, and 23 studies included ≥ 50 patients ^{[10,11,13–18,20,23,25–27,29−32,34,36,38−41]}. The details of baseline information of the included literature were shown in Table 2.

Table 2

Summary of Detailed Information about Included Studies
Author ( year published)	Duration of data collected	Country/ Region	Study design	Numbers of patients	Age (years)	Gender (male/ female)	IABP support (n)
Zhang MH et al. ^[10],2020	2013–2018	China	Retrospective study	60	51.8 ± 12.74	39/21	N/R
Yang F et al. ^[11],2020	2004–2017	China	Retrospective study	139	Survival Group:68(66,70)	98/41	N/R
					Non-survival Group:69(66,72)
Mashiko Y et al. ^[12],2020	2002–2016	Japan	Retrospective study	29	74(75 − 62)	16/13	7
Shao J et al. ^[13],2020	2004–2017	China	Retrospective study	166	61(54–67)	132/34	139
Chen F et al. ^[14],2020	2012–2016	China	Retrospective study	121	62(55–67)	95/26	114
Hou JF et al. ^[15],2019	2006–2017	China	Retrospective study	60	51.4 ± 12.7	45/15	60
Cui YC1 et al. ^[16], 2019	2006–2016	China	Retrospective study	144	Survival Group:54(44,61) Non-survival Group:59(48,66)	93/51	88
Chen K et al. ^[17],2019	2005–2017	China	Retrospective study	152	49.5 ± 14.1	112/40	77
Cui YC2 et al. ^[18], 2019	2006–2016	China	Retrospective study	496	Older Group:68(66,71) Non-older Group:52(44,59)	335/161	277
Li C et al. ^[19],2019	2016–2017	China	RCT	41	58.8 ± 10.5	23/18	N/R
Ge M et al. ^[20],2019	2010–2017	China	Retrospective study + Prospective study	72	Delayed ECMO Group:57.31 ± 16.90 Early ECMO Group:61.17 ± 12.22	43/29	N/R
Wu F et al. ^[21],2019	2011–2018	China	Retrospective study	31	ECMO Group:58 ± 12	16/15	13
					ECMO + IABP Group:64 ± 12
Du Z et al. ^[22],2018	N/R	China	Prospective study	17	59[49-63.5]	12/5	14
Yang F et al. ^[23],2018	2004–2015	China	Prospective study	432	With Vascular Complications Group:57(48.3,65.0)	285/147	245
					Without Vascular Complications Group:57(47.3,65.0)
Zhong Z et al. ^[24],2017	2009–2016	China	Retrospective study	36	50.4 ± 12.2	33/3	9
Chen SW et al. ^[25],2017	2000–2011	Taiwan, China	Retrospective study	1137	63.8 ± 13.2	810/327	728
Zhang BW et al. ^[26],2016	2008–2015	China	Retrospective study	88	52.83 ± 8.10	46/42	N/R
Wang H et al. ^[27],2016	2011–2013	China	Retrospective study	125	Nosocomial Infection Group:54.3 ± 11.2	85/40	73
					Non-infection Group:54.8 ± 12.9
Li CL 1 et al. ^[28],2015	2011–2013	China	Retrospective study	29	Survival Group:44.3 ± 12.1 Non-survival Group:58.5 ± 9.8	20/9	12
Li CL 2 et al. ^[29],2015	2011–2012	China	Retrospective study	69	Survival Group:50.9 ± 12.1 Non-survival Group:58.4 ± 13.1	50/19	43
LI CL 3 et al. ^[30],2015	2011–2012	China	Retrospective study	123	56.2 ± 11.8	81/42	73
Ding XC et al. ^[31],2015	2011–2014	China	Retrospective study	119	Older Group:69.4 ± 3.5 Non-older Group:55.1 ± 6.6	93/26	108
Jiang CJ et al. ^[32],2014	2004–2013	China	Retrospective study	58	Survival Group:57.0 ± 9.8 Non-survival Group:62.9 ± 8.3	43/15	53
Du ZT et al. ^[33],2014	2012–2012	China	Retrospective study	43	59 ± 12.2	30/13	30
Wang JG et al. ^[34],2013	2004–2011	China	Retrospective study	87	65 ± 7	51/36	41
Unosawa S et al.^[35],2013	1992–2007	Japan	Retrospective study	47	64.4 ± 12.5	35/12	41
Li JW et al. ^[36],2011	2004–2008	China	Retrospective study	50	50.5 ± 13.7	38/12	10
Yu K et al. ^[37],2010	2004–2010	China	Retrospective study	12	55.5(35 ~ 72)	9/3	12
Wu MY et al. ^[38],2010	2003–2009	Taiwan, China	Retrospective study	110	Survival Group:54.8 ± 17.5 Non-survival Group:64.6 ± 9.6	78/32	N/R
Wang J et al.^[39],2009	2004–2008	China	Retrospective study	62	51 ± 15	32/30	19
Hsu PS et al. ^[40],2009	2002–2006	Taiwan, China	Retrospective study	51	63.0 ± 15.7	36/15	51
Ko WJ et al. ^[41], 2002	1994–2000	Taiwan, China	Retrospective study	76 (72 for PCCS,4 for bridging heart transplantation.)	56.8 ± 15.9	48/28	54

4.2 Quality Assessment

Due to the ethical issues involved in the study, it is not appropriate to use a placebo-controlled randomized controlled trial. The included literature is mainly observational research. The scores of the 16 observational studies ranged from 6–9 points, indicating that the methodological quality is high ^{[13–15,17,21,24,25,28,30,33–36,38−40]}. Only one randomized controlled trial was included ^[19], it used RRT as control intervention and the methodological quality is high. Details of quality evaluation for each study are shown in Table 3 and Table 4.

Table 3

Modified Jadad’s Scores Scale for RCT
Study	Randomization (2)	Concealment (2)	Blinded (2)	With or drop-out (1)	Total (7)
Li C et al. 2019	2	2	0	1	5

Table 4

The modified Newcastle-Ottawa scale for observational studies
Study	Representativeness of the Population of PCCS Patients Receiving ECMO	Consecutive Patients Included	PCCS Well- Defined	Assessment of Outcome Well-Performed	Primary and Secondary Outcomes Well-Defined	Complications Well-Defined	Follow-Up Long Enough for Outcomes to Occur	Adequacy of Follow up of patients	Total
	*	**	*	*	**	*	*	*	****** ***
Zhang MH et al. 2020			*	*	*		*		********
Yang F et al. 2020			*	*	*	*	*		*****
Mashiko Y et al. 2020	*			*	*	*	*		*****
Shao J et al. 2020	*	*	*	*	*	*	*		*******
Chen F et al. 2020	*	*	*	*	**	*	*	*	*********
Hou JF et al. 2019		*	*	*	**	*	*	*	********
Cui YC1 et al. 2019			*	*	*	*	*		*****
Chen K et al. 2019		*	*	*	*	*	*		******
Cui YC2 et al. 2019			*	*	*	*	*		*****
Ge M et al. 2019	*		*		*	*	*		*****
Wu F et al. 2019	*	*		*	*	*	*		******
Du Z et al. 2018			*		*		*		*******
Yang F et al. 2018	*			*	*	*	*		*****
Zhong Z et al. 2017	*		*	*	*	*	*		******
Chen SW et al. 2017	*			*	**	*	*	*	*******
Zhang BW et al. 2016			*		*	*	*		********
Wang H et al. 2016			*		*	*	*		********
Li CL 1 et al. 2015	*		*	*	*	*	*		******
Li CL 2 et al. 2015			*	*	*	*	*		*****
LI CL 3 et al. 2015	*		*	*	*	*	*		******
Ding XC et al. 2015			*		*	*	*		********
Jiang CJ et al. 2014			*	*	*	*	*		*****
Du ZT et al. 2014	*		*	*	**	*	*	*	********
Wang JG et al. 2013	*		*	*	**	*	*	*	********
Unosawa S et al.2013			*	*	**	*	*	*	*******
Li JW et al. 2011	*		*	*	*	*	*		******
Yu K et al. 2010				*	*	*	*		********
Wu MY et al. 2010	*			*	**	*	*	*	*******
Wang J et al.2009	*		*	*	**	*	*	*	********
Hsu PS et al. 2009	*		*	*	**	*	*	*	********
Ko WJ et al. 2002	*			*	*		*		********

4.3 Primary Outcome: Survival Rate to Hospital Discharge

Cumulative analysis showed that the pooled survival rate to hospital discharge was 43.0% (95% CI 38–47%, I² = 87%). A subgroup analysis of the included patients ≥ 50 showed that the pooled discharge survival rate was 45% (95% CI 40%~50%, I² = 90%). (Fig. 2 and Fig. 3).

Table 5 Meta-analysis of Secondary Outcomes and Publication Bias

(should be appeared in Line189)

Outcomes	Proportion 95% CI	I²(%)	Egger’s p
1-y survival rate	0.34(0.26;0.42)	85%
2-y survival rate	0.29(0.18;0.39)	93%
3-y survival rate	0.25(0.16,0.35)	93%
bleeding	0.18(0.13;0.24)	91%	0.01366
Neurologic complication	0.13(0.09;0.17)	90%	0.003746
Rethoracotomy	0.36(0.27;0.46)	97%	0.003237
Leg ischemia	0.11(0.09;0.13)	55%	0.005572
Renal failure	0.40(0.27;0.54)	90%
Renal replacement therapy	0.45(0.35;0.56)	98%	0.9895
Infection	0.26(0.20;0.31)	95%	0.0001707

4.4 Secondary Outcomes

Major morbidities reported in studies include bleeding, neurologic complications, rethoracotomy, leg ischemia, renal failure and infection. We exhibited information on the meta-analyses results on long-term survival rate and incidence of complication in Table 5. Nine studies (n = 1718) reported 1-year survival rate, and the pooled 1-year survival rate was 34% (95% CI 26% ~ 42%, I² = 85%). Six studies (n = 1577) reported 2-year survival, and the pooled 2-year survival rate was 29% (95% CI 18% ~39%, I² = 93%). Seven studies (n = 1624) reported a 3-year survival rate, and the pooled 3-year survival rate was 25% (95%CI 16 % ~35%, I² = 93%).Major morbidities reported in studies include bleeding, neurologic complications, rethoracotomy, leg ischemia, renal failure and infection. Forest plots of secondary outcomes are shown in Supplementary 1.

4.5 Publication Bias

To assess publication bias, Egger's test was performed (Table 5). Survival rate to hospital discharge (Egger's p = 0.2809) and renal replacement therapy (Egger's p = 0.9895) have low possibility of publication bias, bleeding, neurological complications, rethoracotomy, leg ischemia and infection have higher publication bias.

4.6 Sensitivity Analyses

In order to assess the stability of the results, we conducted sensitivity analyses. The omission of each study of the following outcomes showed no significant difference, confirming the stability of the results: survival rate to hospital discharge, 2-year survival rate, 3-year survival rate, bleeding, rethoracotomy, renal replacement therapy, infection. In the 1-year survival rate and neurological complications, the omission of the Chen SW study showed a significant difference, the omission of the Wu F study in leg ischemia showed a significant difference, and the omission of the Hsu PS study in renal failure showed a significant difference. The results of sensitivity analysis are shown in Supplementary 2.

Cardiogenic shock is a serious complication after cardiac surgery. For patients who do not respond well to inotropic drugs or IABP support, mechanical circulatory support should be used in order to reduce mortality rate. ECMO is one of the extracorporeal life support systems, and relative research started in the 1960s ^{[42, 43]}. The application of ECMO for cardiogenic shock after cardiac surgery have emerged since 1980s ^[44].

As we mentioned earlier, the published systematic reviews on ECMO for PCCS have not considered the impact of race-specific factors and the issue of heterogeneity. Our study is the first one to propose a systematic review and meta-analysis of the pooled survival rate to hospital discharge, long-term survival rate and incidence of complication among Asian patients with PCCS using ECMO treatment. We found the pooled survival rate to hospital discharge of Asian PCCS patients who received ECMO intervention is 43%, which is significantly higher than that of mixed races (30.8%-34%) ^{[5, 7]}, and the pooled 1-year survival rate (34%, 95% CI 26% ~ 42%, I² = 85%) and the pooled 3-year survival rate (25%, 95%CI 16% ~35%, I² = 93%) are higher than the outcome reported by Wang L et al. ^[7]. At the same time, the pooled rate of leg ischemia (11%, 95% CI 9% ~13%, I² = 55%), the pooled rate of rethoracotomy (36%, 95% CI 27% ~46%, I² = 97.0%), renal failure (40%, 95% CI 27% ~54%, I² = 90%), neurological complications (13%, 95% CI 9% ~17%, I² = 90.0%), infection (26%, 95%CI 20 %~31%, I² = 95%) are also lower than the complication rate reported by Wang L et al. ^[7].

The difference of these outcomes between our study and previous studies could be the result of racial differences. Unlike other studies, our study only included Asian populations. Race can have an impact on the efficacy of the use of ECMO. Vallabhajosyula S et al. ^[45] conducted a retrospective cohort to evaluate the efficacy of ECMO for acute myocardial infarction (AMI) between 2000 and 2014 in the USA. One of the conclusions was that compared with whites, non-whites were related with higher in-hospital mortality with ECMO patients. One of the reasons was that non-whites often have insufficient insurance and come from lower socio-economic status. Our study included research mainly from China and Japan, in which ECMO treatment can only be carried out in the economically developed areas with high medical standards. Patients in these areas are more likely to have insurance and higher socio-economic status. Thus, our conclusion can have practical significance for PCCS patients in Asian with regard to the use of ECMO.

In this study, it is found that renal failure is the most common complication in all morbidity, and the rate of renal replacement therapy is quite high. This conclusion is similar to previous meta-analysis. Research on the timing of the application of RRT has found that early RRT treatment for PCCS patients with ECMO is beneficial to the recovery and improves the prognosis ^{[26] [28]}.

The subgroup analysis was performed on the studies with the number of patients ≥ 50, and the pooled discharge survival rate was 45% (95% CI 40%-50%, I² = 90%). It is speculated that as the sample size increases, the medical staff will become more proficient in the indications and operating specifications of the ECMO technology, thereby improving the survival rate of discharge from the hospital. However, the discharge survival rate of study by Chen SW ^[25], which sample size was 1137, was significantly lower than the pooled discharge survival rate (38% VS. 43%). The possible reason was that the study included patients between 2000 and 2011, with a long time span. In the early stage, the immaturity of the technology and the inappropriate selection of indications for PCCS with ECMO may reduce the survival rate. At the same time, we found that the two systematic reviews by Khorsandi M et al. ^[5] and Wang L et al. ^[7] were mostly enrolled patients before 2015, and there were many studies from the 1990s (45.83% and 35%). Comparing with these two systematic reviews, most studies enrolled by our systematic review were conducted after 2015. It can reasonably conclude that with the development of technology and the improvement of medical staff’s skills, the outcome of patients definitely will be improved.

The study by Wu F et al. ^[21] showed the lowest survival rate (16%) and the study of Zhang BW et al. ^[26] showed the highest survival rate (81%). Wu F et al. ^[21] included patients after valvular surgery, which meant these patients had abnormal heart structures or other injuries. Hou JF et al. ^[15] indicated that ECMO was better for patients with PCCS after heart transplantation. The PCCS of these patients mainly caused by cold ischemia and ischemia-reperfusion injury in the donor heart, rather than structural abnormalities or other injuries. Zhang BW et al. ^[26] included patients, whose treatment time with ECMO were over 48h. In the early stage of ECMO application (within 12 hours), if the patient’s hemodynamics is not improved, death is very likely to occur. The study may artificially exclude potentially dying patients, resulting in a higher survival rate.

There are some limitations to this study. First of all, the included studies are mostly observational studies, and the level of evidence are not high, and there is a high risk of selection bias and publication bias. The methodological quality of the included studies was evaluated, and 17 studies were of high quality. The publication of outcomes such as bleeding, neurological complications, rethoracotomy, leg ischemia, and infection are likely to be biased. Second, there are differences in the characteristics of patients in the included studies. Three of the studies included mainly older patients ^{[11] [18] [31]}; the patients included in the studies all used IABP and ECMO at the same time ^{[15] [37]}; two studies included patients treated with renal replacement therapy ^[28]. The underlying diseases of the patients are also different. In the Hsu PS study ^[40], 31% of patients had renal insufficiency before surgery, which was higher than that reported in other studies. The omission of this study in the sensitivity analysis showed the renal failure rate was significantly reducing in pooled result, which indicated those who suffered from renal dysfunction before operation should be under intensive monitoring. In addition, there are differences in the surgical methods adopted among enrolled studies. For example, we found that omitted the valvular surgery patients ^[21] from pooled result led to reduce of heterogeneity and leg ischemia occurrence. The number of patients included is also quite different. The minimum number of patients included is 12^[37], and the maximum number of patients is 1137^[25], which is far higher than the other studies. In the sensitivity analysis, the omissions of the study with 1137 patients about 1-year survival rate and neurological complications showed greatly decreased in I² (62.9% VS. 85%, 66% VS.90%).As we mentioned above, this largest study contained many patients in early stage of ECMO development that reflex the learning curve and development curve of this technology, and cannot represent current status.

ECMO can provide survival benefits for Asian adult patients with PCCS, including short-term and long-term survival. However, attention should be paid to reducing the incidence of complications, especially renal failure. More high-quality clinical studies are needed to confirm these benefits.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and material

All data generated or analyzed during this study are included in this published article (showed in Reference 10-41).

Competing interests

The authors declare that they have no competing interests.

Funding

This work was supported by Sichuan Science and Technology Program [grants IDs 2019YFS0534, to Jun Zeng, and 2019YFS0303, to Ping Zhou, and 2020YFS0392, to Hua Jiang]

Author’s contributions

Dihuan Li took responsibility for the accuracy of the data analysis and wrote the paper. Mingwei Sun extracted data and prepared the figures and tables. Ting Li, Ting Yuan, and Yu Wang searched the database and screened records. Ping Zhou, Jun Zeng, and Hua Jiang designed the study and revised the manuscript.

Acknowledgements

We would like to thank Dr. Charles Damien Lu of Los Angeles Mental Health Center for English language editing.

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Extra-Corporeal Membrane Oxygenation (ECMO) for Postcardiotomy Cardiogenic Shock (PCCS) in Asian Patients: A Systematic Review and Meta-Analysis

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Abstract

Figures

1 Background

2 Objective

3 Methods

3.1 Criteria for considering studies for this review

3.1.1 Types of participants: Asian adult patients with PCCS.

3.1.2 Types of interventions: treatment with ECMO.

3.1.3 Types of studies: retrospective studies, prospective study, randomized controlled trial (RCT).

3.1.4 Types of outcome measures

3.1.4.1 Primary outcomes: survival rate to hospital discharge.

3.1.4.2 Secondary outcomes: long-term survival rate (1-year, 2-year, 3-year survival rate), complications.

3.2 Search methods for identification of studies

3.3 Selection of Studies and Data Extraction

3.4 Quality Assessment

3.5 Statistical Analyses

4 Results

4.1 Search Results and Study Characteristics

4.2 Quality Assessment

4.3 Primary Outcome: Survival Rate to Hospital Discharge

4.4 Secondary Outcomes

4.5 Publication Bias

4.6 Sensitivity Analyses

5 Discussion

6 Conclusion

Declarations

References

Supplementary Files

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