Nosocomial Infection in Patients Treated with Venoarterial Extracorporeal Membrane Oxygenation: Incidence, Risk factors, and Outcomes

doi:10.21203/rs.3.rs-5002180/v1

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Research Article

Nosocomial Infection in Patients Treated with Venoarterial Extracorporeal Membrane Oxygenation: Incidence, Risk factors, and Outcomes

https://doi.org/10.21203/rs.3.rs-5002180/v1

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Background

The success rate of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is related to complications such as nosocomial infection (NI), with multidrug-resistant organisms (MDROs) infection posing the toughest challenge, however, the incidence, risk factors, and prognosis of NI during VA-ECMO are unclear.

Methods

We performed a single-center, retrospective analysis of 152 patients receiving VA-ECMO. Patients were categorized into NI and non-NI groups, depending on whether pathogenic microorganisms were isolated between 48h after VA-ECMO initiation and within 24h weaning from VA-ECMO. Multivariate logistic regression analysis was performed to identify the independent risk factors of NI.

Results

The incidence of NI during VA-ECMO was 38.82% (59/152), and 71 microbial strains were isolated from the cultures, with Gram-negative bacteria accounting for 73.24% (52/71) and MDROs for 63.38% (45/71). The chi-square test showed that the probability of percutaneous dilatational tracheotomy (PDT) was elevated in the NI group (25.42% vs 8.6%). The rank sum test found that the NI group had longer hospitalization (18 vs 12 days), intensive care unit (ICU) stay (16 vs 9 days), and duration of VA-ECMO (6.63 vs 5.01 days), and invasive mechanical ventilation (IMV, 11 vs 6 days). Multivariate logistic regression analysis revealed that the occurrence of NI was independently associated with ICU stay (OR 1.128; 95%CI 1.004 ~ 1.268; P = 0.043) and the need for PDT (OR 3.459; 95%CI 1.051 ~ 11.389; P = 0.041).

Conclusions

The Gram-negative bacilli was the most common pathogens for NI during ECMO, with MDROs being the predominant species. The occurrence of NI in patients caused a prolonged ICU stay and increased probability of PDT.

Trial registration

ChiCTR1900026105 (Registration Date 20190921).

Venoarterial extracorporeal membrane oxygenation

Nosocomial infection

Multidrug-resistant organisms

Invasive mechanical ventilation

Percutaneous dilatational tracheotomy

As a bridging therapy, venoarterial extracorporeal membrane oxygenation (VA-ECMO) can temporarily replace cardiopulmonary function, giving time for the treatment of primary diseases and recovery of cardiopulmonary function [1, 2]. Potential complications during ECMO, such as infection, bleeding, and embolism, may lead to poor prognosis [3, 4]. In particular, nosocomial infection (NI) may be associated with high mortality, with multidrug-resistant organisms (MDROs) infection being the most serious challenge [5, 6]. The incidence of NI in adult ECMO patients can be > 20%, which is higher than that in neonatal and pediatric patients (6.1%) [5]. It has also been demonstrated that NI in patients receiving VA-ECMO treatment after cardiac surgery may be significantly associated with duration of VA-ECMO, prolonged duration of VA-ECMO support was an independent risk factor for NI [7]. Several studies have focused on the distribution of pathogens causing NI in ECMO patients, as well as drug resistance [8, 9]. To date, only a few studies on the risk factors for secondary NI in adult peripheral VA-ECMO patients and their impact on prognosis have been reported [5, 8].

In light of potential misinterpretation of the organism cultural results, patients receiving venovenous-ECMO were not enrolled. Because most cases of the VV-ECMO group were diagnosed with severe pneumonia. And the presence of microorganisms maybe responsible for the infective disease and could not attribute to NI [10, 11]. In this study, we retrospectively analyzed the clinical data of patients treated with VA-ECMO at the Extracorporeal Life Support Center of the First Affiliated Hospital of Nanjing Medical University to investigate the incidence, risk factors, and isolated bacterial flora of NI and their impact on clinical prognosis.

This study retrospectively analyzed the clinical data of 210 patients who underwent VA-ECMO at the Extracorporeal Life Support Center of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial Hospital) between January 2020 and August 2023. The inclusion criteria were: (1) patients with cardiac arrest or refractory cardiogenic shock who met the guidelines for VA-ECMO issued by the Extracorporeal Life Support Organization (ELSO); (2) VA-ECMO duration of at least 48h; and (3) peripheral VA-ECMO. Patients who met one or more of the following criteria were excluded: (1) treatment time < 48h; (2) cardiac arrest or refractory cardiogenic shock caused by infective diseases; (3) Admission in intensive care unit(ICU) within 1 year; (4) incomplete medical records; (5) VA-ECMO withdrawal on the request of family members; and (6) pregnancy [1, 2]. This study was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial Hospital) (Number: 2020-SR-226).

NIs during VA-ECMO were defined as infections in which the presence of microorganisms such as bacteria and fungi was confirmed from one or more cultures of blood, sputum, and other body fluids between 48h after VA-ECMO initiation and weaning from VA-ECMO within 24h [4, 8]. The microorganisms that have developed resistance to one or more classes of antimicrobial agents are defined as MDROs [12, 13]. In this case, correlation of isolated microorganisms with clinical symptoms, blood inflammatory indicators, and imaging findings was jointly confirmed by two clinicians; one expert in microbial identification and one pharmacist. Patients were categorized into the NI and non-NI groups based on whether or not definitive microorganisms were isolated and cultured from body fluid. The following information was collected for each case: (1) general information such as patient’s age, height, weight, and body mass index, comorbidity, primary disease, Acute physiology and chronic health evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) scores, as well as the presence or absence of NI, and isolated microbial strains and collection sites; (2) initial values of tests conducted within 1 hour after successful VA-ECMO, including arterial blood gases, routine venous blood analysis, biochemical indicators, procalcitonin (PCT), and C-reactive protein (CRP); (3) clinical data about whether extracorporeal cardiopulmonary resuscitation was applied, VA-ECMO catheterization time, placement of distal perfusion catheter, and the need for continuous renal replacement therapy (CRRT), Invasive mechanical ventilation (IMV), and Intra-aortic ballon pump (IABP) treatment prior to infection; and (4) main prognostic parameters including 28-day mortality, duration in ICU, length of hospitalization, duration of VA-ECMO, IMV, and CRRT, and the need for percutaneous dilatational tracheostomy (PDT).

Statistical analysis was performed using R4.1.3 software. Quantitative data that followed a normal distribution were expressed as mean ± standard deviation, and differences between groups were assessed using independent samples t test. Quantitative data that did not follow a normal distribution were presented as medians and quartiles, and differences between groups were compared using the Wilcoxon rank sum test. Frequencies and component ratios were used to describe the distribution of qualitative data, and differences between groups were compared using chi-square tests. Multivariate logistic regression analysis was performed to identify the independent influencing factors of NI. All tests in this study were two-sided, and P < 0.05 was considered significant.

We collected clinical data from 210 patients. Fifty-eight were excluded due to VA-ECMO duration < 48h (n = 26); confirmed bacterial or fungal infection prior to VA-ECMO, or admission to ICU before hospitalization (n = 20); incomplete medical records (n = 6); VA-ECMO withdrawal on the request of family members (n = 4); or pregnancy (n = 2). Finally, 152 patients were included in the statistical analysis. These patients had an average age of 49.9 ± 14.81 years, with 68.42% (104) being male, and a median ECMO duration of 5.7 days (Table 1). Independent sample t test revealed no significant differences in age, height, weight, or BMI between the NI group (n = 59) and non-NI group (n = 93). The chi-square test showed that there were no significant differences between the two groups in terms of gender, comorbidity (previously confirmed hypertension, coronary heart disease, chronic lung disease, diabetes, tumors, and immune system disorders), primary disease, whether extracorporeal cardiopulmonary resuscitation was performed, whether distal perfusion tubes were placed, and whether IMV, CRRT, or IABP was needed prior to infection. Likewise, the rank sum test showed that there were no significant differences in APACHE II and SOFA scores, or VA-ECMO catheterization time between the two groups.

Table 1

Comparison of baseline characteristics between the nNI and NI groups
Baseline characteristics	non-NI	NI	Statistical value	p-value
Gender(M/F)	62/31	42/17	0.341	0.559
Age(y)	50.51 ± 14.9	48.95 ± 14.75	0.632	0.529
Height (cm)	169.39 ± 7.4	168.85 ± 8.24	0.409	0.683
Weight (Kg)	70.57 ± 14.03	73.12 ± 16.17	-0.995	0.322
BMI(Kg/m² )	24.48 ± 3.95	25.52 ± 4.64	-1.421	0.158
Comorbidities, n (%)
Hypertension	33(35.48)	14(23.73)	2.335	0.126
Coronary artery disease	12(12.9)	5(8.47)	0.713	0.399
Chronic lung disease	3(3.23)	0(0)	—	0.283
Diabetes Mellitus	17(18.28)	8(13.56)	0.585	0.444
Tumors	3(3.23)	2(3.39)	—	> 0.999
Immune system disorders	0(0)	2(3.39)	—	0.149
Protopathy, n (%)			0.900	0.825
AMI	49(52.69)	30(50.85)
FMC	26(27.96)	19(32.2)
PE	8(8.6)	3(5.08)
Others	10(10.75)	7(11.86)
ECPR, n (%)	49(52.69)	34(57.63)	0.355	0.551
Distal perfusion tubes, n (%)	42(45.16)	32(54.24)	1.190	0.275
IMV, n (%)	80(86.96)	55(93.22)	1.489	0.222
CRRT, n (%)	53(56.99)	33(55.93)	0.016	0.898
IABP, n (%)	27(29.03)	11(18.64)	2.078	0.149
Catheterization time, IQR (Q1, Q3), (min)	30(19,35)	30(25,40)	-1.852	0.064
APACHE II, IQR (Q1, Q3)	31(25,36)	32(22,37)	-0.053	0.958
SOFA, IQR (Q1, Q3)	12(10,14.25)	12(10,14)	-0.767	0.443
Body mass index(BMI), Acute myocardial infarction(AMI), Fulminant myocarditis(FMC), Pulmonary embolism(PE), Extracorporeal cardiopulmonary resuscitation (ECPR), Invasive mechanical ventilation (IMV), Continuous renal replacement therapy(CRRT), Intra-aortic ballon pump (IABP), Acute physiology and chronic health evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA).

The independent sample t test of blood testing indicators found no significant difference in pH between the two groups (Table 2). The rank sum test showed that the two groups had no significant differences in initial white blood cell count, proportion of neutrophils, proportion of lymphocytes, platelet count, alanine aminotransferase, aspartate aminotransferase, creatinine, urea nitrogen, albumin, troponin T, brain natriuretic peptide, partial thromboplastin time, fibrinogen, PCT, CRP, blood glucose or lactate.

Table 2

Comparison of laboratory test between the nNI and NI groups
Laboratory test	non-NI	NI	Statistical value	p-value
White blood cell (×10⁹/L)	16.13(10.59,21.24)	15.89(10.68,20.23)	-0.433	0.665
Neutrophils (%)	84.7(78.8,88.84)	84.1(80.05,88)	-0.624	0.533
Lymphocytes (%)	8.7(5.8,14.3)	9.4(6.65,12.86)	-0.605	0.545
Platelet (×10⁹/L)	158(110,211)	181(135.5,237.5)	-1.261	0.207
ALT (µmol/L)	173.1(72.7,455.1)	181.5(63.85,538.15)	-0.036	0.971
AST (µmol/L)	412.4(114.9,1006.6)	467.7(139.8,956.8)	-0.106	0.916
Creatinine (µmol/L)	110.3(79.6,155.7)	103(83.85,145)	-0.520	0.603
Urea nitrogen (mmol/L)	7.89(5.8,11.86)	7.25(5.74,9.93)	-0.794	0.427
Albumin (g/L)	31.2(27.1,38.5)	31.7(28.6,35.35)	-0.106	0.916
Troponin T (µmol/L)	2740(588.9,9224)	3034(640.35,6945.5)	-0.371	0.710
BNP (pg/mL)	4045.8(631.7,13808.8)	3591(955.5,12623.8)	-0.306	0.759
APTT (s)	43.7(32.8,100.1)	41.6(30.05,66.4)	-1.437	0.151
Fibrinogen (g/L)	2.14(1.37,3.88)	2.26(1.58,3.86)	-0.501	0.616
Procalcitonin (ng/mL)	2.18(0.27,5.57)	1.43(0.21,7.72)	-0.509	0.611
CRP (mg/L)	39(7.6,84.2)	31.05(11.25,77.67)	-0.125	0.901
Blood glucose (mmol/L)	9(6.8,15.45)	11.3(8.2,14.4)	-1.747	0.081
pH	7.32 ± 0.20	7.31 ± 0.20	0.365	0.716
Lactate (mmol/L)	5.49(3.09,10.41)	5.22(2.35,10.05)	-0.316	0.752
Alanine aminotransferase (ALT), Aspartate aminotransferase (AST),Brain natriuretic peptide (BNP), Activated partial thromboplastin time (APTT), C-reactive protein (CRP).

The chi-square test found that while there was no significant difference in 28-day mortality between the two groups, the probability of PDT in the NI group was greater than that in the non-NI group (25.42% vs 8.6%, P = 0.005). The rank sum test showed that the NI group had longer duration of hospitalization (18 vs 12 days, P = 0.002), time in ICU (16 vs 9 days, P < 0.001), duration of VA-ECMO (6.63 vs 5.01 days, P < 0.001), and duration of IMV (11 vs 6 days, P < 0.001) than the non-NI group. In contrast, there was no significant difference in duration of CRRT between the two groups (Table 3). Multivariate logistic regression analysis was performed to investigate the independent risk for of NI. NI was not associated with hospitalization days and duration of IMV and VA-ECMO, but it was independently associated with time in ICU (OR 1.128; 95%CI 1.004 ~ 1.268; P = 0.043) and the need for PDT (OR 3.459; 95%CI 1.051 ~ 11.389; P = 0.041) (Table 4). These results indicated that the occurrence of NI led to significantly prolonged duration of ICU stay and markedly increased probability of needing PDT.

Table 3

Comparison of prognosis between the nNI and NI groups
Prognosis	non-NI	NI	Statistical value	p-value
28-day mortality, n (%)	45(48.39)	38(64.41)	3.737	0.053
Length of ICU stay(d)	9(5,15)	16(11,25.5)	-4.173	0.000**
Hospitalization days(d)	12(5,20)	18(11.5,29)	-3.170	0.002*
PDT, n (%)	8(8.6)	15(25.42)	7.954	0.005*
Duration of VA-ECMO(d)	5.01(3.56,6.97)	6.63(5.34,9.29)	-3.773	0.000**
Duration of IMV(d)	6(3,9)	11(7,15)	-4.156	0.000**
Duration of CRRT(d)	3(0,7)	6(0,13.5)	-1.784	0.074
Intensive care unit (ICU), Percutaneous dilatational tracheostomy (PDT), Venoarterial extracorporeal membrane oxygenation (VA-ECMO), Continuous renal replacement therapy (CRRT), Invasive mechanical ventilation (IMV). * p<0.05, ** p<0.001.

Table 4

Multivariate logistic regression analysis for NI during ECMO support.
	B	SE	Wald	OR(95%CI)	P
PDT	1.241	0.608	4.166	3.459(1.051 ~ 11.389)	0.041*
Length of ICU stay(d)	0.121	0.060	4.114	1.128(1.004 ~ 1.268)	0.043*
Hospitalization days(d)	-0.017	0.030	0.325	0.983(0.927 ~ 1.042)	0.569
Duration of IMV	-0.044	0.030	2.154	0.957(0.902 ~ 1.015)	0.142
Duration of VA-ECMO	0.019	0.032	0.356	1.020(0.957 ~ 1.087)	0.551
Percutaneous dilatational tracheostomy (PDT), Intensive care unit (ICU), Invasive mechanical ventilation (IMV), Venoarterial extracorporeal membrane oxygenation (VA-ECMO). * p<0.05,

We further showed that the incidence of NI during VA-ECMO was 38.82% (59/152), with a total of 71 microbial strains being isolated from the cultures. Multiple microorganisms or microorganisms cultured from multiple sites were isolated in 12 of 59 cases, and most of the isolated microbial strains (88.73%, 63/71) were cultured from qualified lower respiratory tract specimens. The main isolated microbial strains were Gram-negative bacteria, accounting for 73.24% (52/71) (Table 5). Klebsiella pneumoniae, Acinetobacter baumannii, and Stenotrophomonas maltophilia were the top three isolated bacteria. Among the isolated microbial strains, fungi accounted for 18.31% (13/71), with Candida albicans being the most abundant (9/71, 12.68%). MDROs accounting for 63.38% (45/71) of the isolated microbial strains.

Table 5

Microbial strains and sites for NI during ECMO support.
Microbial	Lower respiratory tract	Blood	Urinary	Total
Klebsiella pneumoniae	18	/	1	19
Acinetobacter baumannii	10	1	1	12
Stenotrophomonas maltophilia	8	/	/	8
Klebsiella aerogenes	5	/	/	5
Burkholderia cepacia	3	/	/	3
Pseudomonas aeruginosa	1	/	1	2
Serratia marcescens	2	/	/	2
Escherichia coli	1	/	/	1
Staphylococcus aureus	3	1	/	4
Enterococcus faecium	/	1	1	2
Candida albicans	8	/	1	9
Candida glabrata	2	/	/	2
Aspergillus flavus	1	/	/	1
Kodamaea ohmer	1	/	/	1

The median time for the occurrence of NI during VA-ECMO was 5 (3–7) days. A time–frequency histogram was constructed using the occurrence time of NI as the abscissa and frequency as the ordinate. The peak period for NI occurrence was 2–5 days after initiation of VA-ECMO, accounting for 50.85% (Fig. 1). After that, the daily frequency of NI gradually decreased until a second peak occurred in 2–3 weeks, totaling about 6.78%.

VA-ECMO is becoming more widely used for reversible cardiopulmonary failure, and its success rate is not only related to the primary disease, but also closely related to complications such as NI, bleeding, and thrombosis [3, 4]. There is still controversy over whether NI increases the mortality rate of ECMO patients. A retrospective study based on ELSO registry data showed that the mortality rate of adult NI patients receiving ECMO was significantly higher than that of non-NI patients (57.6% vs 41.5%). Given that these two studies with the same data source excluded many cases with incomplete data, the results remain inevitably controversial [14, 15]. A meta-analysis found that NI increased the relative risk of death by 32% in adult patients treated with ECMO [16]. However, some studies have concluded that there is no significant difference in in-hospital mortality between NI and non-NI groups during ECMO [4, 8]. In the present study, intergroup comparison revealed that compared with the non-NI group, the 28-day mortality rate was not significantly increased in the NI group. To date, the evidence from many current studies on the relationship between NI and ECMO in-hospital mortality remains insufficient and equivocal [4, 8, 14, 15]. Hence, further investigation is needed, and more rigorous prospective multicenter randomized controlled studies or larger studies are required to obtain more definitive evidence.

Previous studies have shown that the occurrence of NI during ECMO may prolong the duration of ECMO and IMV, thereby affecting the length of hospitalization or ICU stay [16, 17]. Consistently, in the present study, the number of hospitalization days, ICU admission days, PDT probability, duration of ECMO, and duration of IMV were all higher in the NI group than in the non-NI group. Farther, multivariate logistic regression analysis showed that the occurrence of NI was only independently correlated with length of ICU stay and PDT. We observed an increased probability of PDT after the occurrence of NI, which may have been related to the previously reported finding that NI prolongs the duration of IMV. If clinicians determine that a patient is unable to successfully wean from IMV within 2 weeks, they are likely to more aggressively choose PDT [18].

The prevalence of NI in VA-ECMO patients varied among different studies, with the rates of a single-center fluctuating between 9% and 65% [17]. In contrast, the analysis of ELSO registry data found that the overall incidence of NI was 20.9% [14, 15]. We reported that the incidence of NI during VA-ECMO was 38.82% in our center. The large difference in the incidence of NI among these studies may be due to the challenge of diagnosing NI in VA-ECMO patients, as follows: (1) the most important fever symptoms are not easily detected due to the use of heat exchangers; (2) immunogenicity of cannulation and circuit may affect levels of PCT, CRP, and other inflammatory markers; (3) VA-ECMO patients are prone to complications of pulmonary edema, which lead to new pulmonary patchy shadows that are easily confused with pulmonary infections; and (4) while microbiological cultures are currently widely recognized as a diagnostic indicator for NI, there is still a lack of guidelines and recommendations for standardized specimen collection procedures and prevention of infections. Moreover, microbiological cultures may produce false-negative and false-positive results because of inherent defects. Due to the influence of various confounding factors, bacterial culture of body fluids may not be the best representation of NI, although it may still be the most suitable monitoring method [9, 17, 19]. Given the lack of clear guidelines or expert consensus, as well as a lack of standardized specimen collection processes, the design of a rational collection process for body fluid culture could be a research direction in the future. The VA-ECMO circuit may cause an increase in the level of white blood cells, CRP, and PCT through mechanisms involving pan-endothelial damage, leukocyte activation, and proinflammatory responses. However, we believe that a dynamic upward trend of inflammatory markers still represents the possibility of NI. In this case, additional fluid bacterial culture may be necessary.

The NI analysis of the ICU showed that the main site of infection was the lower respiratory tract, with the highest incidence rate reaching 65%, followed by urinary tract and blood [20]. Some studies have suggested that NI during ECMO mainly involves respiratory infections [9, 16], others have shown that the most common infections are blood infections, followed by respiratory and urinary tract infection[15, 21]. The present study identified the highest detection rate of pathogenic microorganisms in the lower respiratory tract (88.73%) during ECMO, followed by blood and the urinary tract. This may be because the probability of IMV in ECMO patients in our center was 88.82%. In these cases, tracheal intubation and IMV can disrupt airway defense mechanisms, and exogenous bacteria or oral–nasal colonization flora are more likely to enter the lower respiratory tract, causing infection. It has also been reported that the incidence of ventilator-associated pneumonia (VAP) in patients administered with ECMO and IMV is higher than that in patients with IMV alone [17]. Alternatively, the unreliable of other clinical factors such as body temperature and inflammatory indicators mentioned above may cause difficulty in distinguishing colonizing bacteria from pathogenic bacteria [9, 17, 19]. In such circumstances, some colonizing bacteria may be mistaken for pathogenic bacteria, resulting in an increase in the detection rate of respiratory infection.

Most studies have suggested that the main pathogenic bacteria for NI during VA-ECMO are Gram negative, including A. baumannii, K. pneumoniae, and Pseudomonas aeruginosa. However, there is significant heterogeneity with regard to specific bacterial species, as each hospital has its own microbiological profile [3, 8, 9]. Consistently, pathogenic bacteria with the highest detection rate (73.24%) in the present study were also Gram negative, with the top two being K. pneumoniae (26.76%) and A. baumannii (16.9%). Recent studies have shown that the detection rate of Candida in hospitals is increasing, but the diagnosis of Candida pneumonia itself is controversial and difficult [9]. The present study also found that the detection rate of fungi was 18.31%, with the rate of C. albicans (12.68%) being the highest. Previous studies have shown that MDROs caused 56% of NI during ECMO [11], while MDROs infection rates were as high as 63% in the present study. Increased detection of MDROs may be attributed to the following risk factors: (1) unreasonable empirical antibiotic use; (2) contact of blood with ECMO circuit and oxygenation pumps may cause a cascade effect of inflammation and immunoglobulin loss; and (3) severely ill patients themselves may be in an immunosuppressive state [9, 22]. We believe that appropriate microbiological surveillance and appropriate empiric anti-infection measures based on microbiology in local centers, as well as strengthening the implementation and improvement of MDROs control measures, are crucial for the prevention and treatment of NI.

A study on pediatric patients treated with VA-ECMO found that the median time of NI was 4 (3–5) days [23]. Bouglé et al. also showed that the median time of the infection in adults administrated with VA-ECMO and VAP was 5 (3–12) days [24]. Likewise, the present study demonstrated that the median time of NI during VA-ECMO was 5 (3–7) days. The fact that NI mostly occurs in the early days of VA-ECMO might be explained by the following three mechanisms. (1) We found that VA-ECMO-related NI mostly occurred in the lower respiratory tract. It has also been suggested that ECMO patients administered with IMV are more likely to be complicated by VAP, and VAP tends to occur in the early stage of IMV [17, 25]. (2) In the early stages of VA-ECMO, the patient’s blood comes into contact with the ECMO cannula and pump, resulting in abnormal immune function in the patient through pan-endothelial damage, leukocyte activation, and proinflammatory responses [9, 17]. (3) Some studies suggest that the infection rate in VA-ECMO patients is directly proportional to their blood flow, and that the flow is maintained at a high level in the early stages of VA-ECMO [26].

This study had some limitations. First, there was difficulty in distinguishing between colonizing and pathogenic bacteria for diagnosing NI during ECMO. Second, this was a single-center retrospective study. The effect of NI on the mortality is still unclear because of the small sample size. Lastly, given the diverse types of cultivated bacteria and fungi, differences in collection sites, drug resistance, and combinations, as well as the large statistical bias, we only listed the bacterial types and cultivation sites without conducting relevant subgroup analysis.

Our study found that the lower respiratory tract was the most common site of microbial detection and the Gram-negative bacilli was the most common pathogens for NI during VA-ECMO, with MDROs being the predominant species. The occurrence of NI in patients caused a prolonged ICU stay and increased probability of PDT, but there were no significant differences in 28-day mortality rate between the two groups.

VA-ECMO, Veno-arterial Extracorporeal Membrane Oxygenation; NI, nosocomial infection; PDT, percutaneous dilatational tracheotomy;ICU, intensive care unit; PCT, procalcitonin; CRP, C-reactive protein;CRRT, continuous renal replacement therapy, IMV, invasive mechanical ventilation; IABP, Intra-aortic ballon pump.

Ethics approval and consent to participate: The study was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (No. 2020-SR-226). Informed consent was signed by legal representatives of all patients before catheterization.

Consent for publication: Not applicable.

Availability of data and materials: The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Competing interests: The authors declare that they have no competing interests.

Funding: This work was supported by the key medical discipline of Jiangsu Province (grant number: ZDXK202213), the top talent training program of Jiangsu Province Hospital (grant number: YNRCZN002), and the Clinical Capacity Enhancement Project of Jiangsu Province Hospital (grant number: JSPH-MC-2022-28).

Authors' contributions: HZ, TD and YTS participated in the design of the study, data reduction and drafted the manuscript. YZ and ZMZ performed the statistical analysis. CC, JRL and YM participated in patient management, data collection and analysis. WL participated in data quality assessment and manuscript revision, XFC conceived the study, manuscript revision and provided financial support. All authors read and approved the final manuscript.

Acknowledgements: We would like to thank all the staff of the emergency center of the First Affiliated Hospital of Nanjing Medical University for their having contributed data. We are also grateful to every member of the ECMO team for their hard work to take care of the patients treated with VA-ECMO in the center.

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Nosocomial Infection in Patients Treated with Venoarterial Extracorporeal Membrane Oxygenation: Incidence, Risk factors, and Outcomes

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