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Risk factors for nosocomial infection in patients undergoing extracorporeal membrane oxygenation support treatment: A systematic review and meta-analysis

  • Xiangui Lv ,

    Roles Conceptualization, Writing – original draft

    ‡ XL and YH have made similar contributions to this manuscript and are co first authors.

    Affiliation Department of Intensive care medicine, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China

  • Yan Han ,

    Roles Writing – review & editing

    ‡ XL and YH have made similar contributions to this manuscript and are co first authors.

    Affiliation Geriatrics Center of Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China

  • Daiqiang Liu,

    Roles Data curation

    Affiliation Department of Intensive care medicine, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China

  • Xinwei Chen,

    Roles Data curation

    Affiliation Department of Intensive care medicine, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China

  • Lvlin Chen,

    Roles Supervision, Writing – review & editing

    Affiliation Department of Intensive care medicine, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China

  • Huang Huang,

    Roles Data curation

    Affiliation Department of Infection, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China

  • Chao Huang

    Roles Data curation, Writing – review & editing

    462442086@qq.com

    Affiliation Department of Intensive care medicine, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China

Abstract

Objective

To evaluate the risk factors of nosocomial infection during Extracorporeal membrane oxygenation (ECMO) treatment through systematic evaluation and meta-analysis, in order to provide evidence-based basis for clinical treatment and prevention of nosocomial infection during ECMO treatment.

Method

Computer search of Cochrane Library, PubMed, Embase, and Web of Science databases was conducted to establish a database of relevant literature published in March 2023. Two researchers independently screened literature, extracted data, and evaluated quality based on inclusion and exclusion criteria, and then analyzed the data using STATA 14.0 software. This plan is registered with PROSPERO as CRD42021271083.

Result

A total of 2955 ECMO patients, including 933 nosocomial infected patients, were included in 23 articles. Meta analysis showed that immunosuppression, Heart transplantation, VA-ECMO, CRRT, red blood cell input, ECMO support time, mechanical ventilation time, ICU hospitalization time, and total hospitalization time were the risk factors for nosocomial infection in patients supported by ECMO.

Conclusion

ECMO treatment for nosocomial infections in patients is related to multiple factors. In clinical work, medical staff should identify high-risk groups of ECMO nosocomial infections, actively take preventive measures, and reduce the incidence and mortality of nosocomial infections.

Introduction

The World Health Organization currently defines nosocomial infection as infections that occur during the care process of a patient in a hospital or other healthcare facility, are not present at admission, or are latent. Ventilator associated pneumonia (VAP) and Bloodstream infection (BSI) are common types of nosocomial infections in critically ill patients [1]. VAP is defined as pneumonia that occurs 48 hours after mechanical ventilation and is a common complication after tracheal intubation in critically ill patients [2]. BSI is defined by positive blood cultures in a patient with systemic signs of infection and may be either secondary to a documented source or primary—that is, without identified origin [3]. Nosocomial infection is one of the most common complications after Extracorporeal membrane oxygenation (ECMO) treatment, and is associated with increased demand for antibiotic treatment and higher nursing costs [1, 4]. Nosocomial infection is a global public health issue, with over 140000 patients worldwide dying from NI every year [5]. ECMO is an advanced respiratory and circulatory support technology widely used as an extracorporeal life support (ECLS) strategy for patients with respiratory and/or heart failure [6]. However, ECMO can cause various complications such as bleeding, thrombosis, and infection during use, leading to a significant increase in mortality rate [7]. A meta-analysis showed that the prevalence of nosocomial acquired infections was 8.8–64.0%, with a 4% increase in mortality risk. Nosocomial acquired infections have been identified as the most common complication among patients receiving ECMO, seriously affecting patient recovery [8]. Nosocomial infection has become a challenge for ECMO weaning. In order to effectively prevent the occurrence of nosocomial infection in patients receiving ECMO support treatment, many scholars have explored the risk factors of nosocomial infection in ECMO support treatment patients, but the results of various studies are inconsistent. At present, there is still a lack of meta-analysis on the risk factors of nosocomial infection in patients receiving ECMO support treatment. This article conducts a systematic evaluation and meta-analysis by collecting research on the risk factors of nosocomial infection in patients receiving ECMO support treatment, aiming to provide evidence-based basis for clinical prevention of nosocomial infection.

Information and methods

Inclusion and Exclusion Criteria for Literature Inclusion Criteria:

Inclusion criteria: publicly published research on risk factors for nosocomial infection during ECMO treatment; The study type is Cohort study or Case–control study; The diagnostic criteria for nosocomial infection are clear; Study subjects were adult patients.

Exclusion criteria: Repeated publications; Incorrect data collection or statistical methods; Review, case reports, and animal experiments.

Research retrieval strategy

A study on the risk factors of nosocomial infection during ECMO treatment, published on March 1, 2023, was conducted through computer retrieval of Cochrane Library, PubMed, Embase, Web of Science, and database creation to retrieval. Use the following keywords: “Extracorporeal Membrane Oxygenations/Membrane Oxygenation, Extracorporeal/ECMO Treatment/Extracorporeal Life Support” “Cross Infections/Hospital Infection/Nosocomial Infection”.

Data extraction

Two researchers (Xiangui Lv and Xinwei Chen) independently completed literature screening and data extraction. If there are different opinions on the literature and data, they will negotiate with the third researcher (Chao Huang) to resolve the issue. The data extraction content includes the author of the included study, country, publication time, follow-up time, sample size, study type, nosocomial infection type, and influencing factors involved.

Quality evaluation of studies

The Newcastle Ottawa Scale (NOS) evaluation criteria were used to evaluate the quality of literature. NOS includes three parts: study population selection, inter group comparability, and exposure factors, with a maximum score of 9 A score of 7 indicates high-quality research, a score of 5–6 indicates medium quality research, and a score of ≤ 4 indicates low-quality research. If there are differences of opinion during the evaluation process, they can be resolved through mutual discussion or consultation with the third researcher.

Statistical analysis

Using STATA 14.0 software for meta-analysis of literature, heterogeneity testing was first conducted. If P>0.1 and I2<50%, it indicates good homogeneity between studies, and a fixed effects model was used for analysis; If P ≤ 0.1 and I2>50%, it indicates heterogeneity between studies, and a random effects model is used for analysis. Count data using OR as an outcome measure, calculate the combined OR value and its 95% CI. The continuous variable uses standardized mean deviation as the effect indicator.

Results

Study retrieval results

In the preliminary screening, a total of 1086 related studies were retrieved. According to the inclusion and exclusion criteria, a total of 23 studies were included, including 2955 ECMO patients, including 933 nosocomial infected patients. The flow chart of literature screening is shown in Fig 1. Basic characteristics of the included literature Table 1, and the results of literature quality evaluation are shown in Table 2

Basic characteristics and bias risk assessment results included in the study

Of the 23 included studies, 22 were retrospective studies and 1 was prospective Cohort study; Published from 1999 to 2023; Distributed in China, the United States, South Korea, France, Australia and Croatia; Five studies with a NOS score of ≥ 7, 16 studies with a score of 5–6, and 2 studies with a score of ≤ 4 were included in the study. Most studies were of medium quality. The basic characteristics of the included study are shown in Table 1, and the results of the risk assessment of bias in the included study are shown in Table 2.

Meta analysis of risk factors for nosocomial infection during ECMO treatment

A total of 34 risk factors were mentioned in 23 articles, of which ≥ 2 articles involved a total of 14 factors. A meta-analysis of 14 risk factors showed that immunosuppression, heart transplantation, VA-ECMO, ECMO support time, mechanical ventilation time, CRRT, red blood cell input, ICU hospitalization time, and total hospitalization time were risk factors for nosocomial infections. The results of the meta-analysis are shown in Table 3.

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Table 3. Meta analysis of risk factors for nosocomial infection during ECMO treatment.

https://doi.org/10.1371/journal.pone.0308078.t003

Other risk factors

In this study, multiple risk factors were only reported in a single literature and cannot be combined with meta-analysis for descriptive analysis. Elevated creatinine levels [17]、Cardiopulmonary resuscitation pumped on time [18]、Bleeding (over 1000ml per transfusion) [19]、ECMO duration>250h[19]、liver failure [22]、renal failure [22]、mechanical complications include oxygenator failure [24]、autoimmune diseases (including systemic lupus erythematosus, Wegener’s granulomatosis, Dermatomyositis, antiphospholipid syndrome and Scleroderma with Vasculitis, etc.) [24]、viral pneumonia [31]、high Sequential Organ Failure Assessment (SOFA) score [28] are risk factors for nosocomial infection in ECMO patients.

Publication bias test

Egger’s test has been used for publication bias testing, and the results indicate that there is no publication bias. The Eggers test results are shown in Table 3

Discussion

Based on the published Cohort study and Case–control study, this Systematic review and meta-analysis explored the potential risk factors of nosocomial infection in patients supported by ECMO, and included subjects from 23 studies. We found that the potential risk factors for nosocomial infection in patients with ECMO support were immunosuppression, Heart transplantation, VA-ECMO, ECMO support time, mechanical ventilation time, CRRT, red blood cell input, ICU hospital stay, and total hospital stay.

There is a correlation between ECMO support time and nosocomial infection. ECMO support for more than 250 hours can significantly increase the incidence rate of BSI. Therefore, it is necessary to carefully evaluate the symptoms and signs of invasive instruments, intubation site wounds, and fever. If the patient has persistent fever and increased white blood cells, especially when the duration of ECMO exceeds 10 days, a complete assessment of sepsis should be conducted [14, 19]. Prolonged mechanical ventilation time is a risk factor for nosocomial infection. During mechanical ventilation treatment, tracheal intubation can damage the natural protective barrier of the respiratory tract, weaken tracheal ciliary movement and cough reflex, which increases the risk of pathogen invasion and further increases the risk of VAP occurrence. [32]. In patients with long-term mechanical ventilation, the respiratory function is significantly degraded, the Pharyngeal reflex and the ability to cough and expectorate are weakened, and the pathogenic bacteria colonized in the oropharynx can invade the lungs through mechanical ventilation, causing infection [33]. Tracheostomy in patients with tracheal intubation can reduce airflow resistance, respiratory force, and sedation needs, while improving patient comfort and mobility [34]. Early tracheostomy in ECMO patients is significantly associated with good patient prognosis, as well as shortened mechanical ventilation, ECMO operation, and ICU hospitalization time [35, 36]. The implementation of tracheostomy during ECMO operation can reduce the incidence of hospital infections and improve patient outcomes.

The prolonged hospitalization time and total hospitalization time in ICU are risk factors for nosocomial infection, which may be related to the more critical condition of patients with prolonged hospitalization time, the relative increase in various treatments and invasive procedures, and the increased chance of infection. When the patient’s condition allows, the length of hospitalization should be minimized as much as possible.

CRRT treatment is a risk factor for nosocomial infections in patients receiving ECMO. ECMO and CRRT support treatment increased significant variability in antibiotic blood concentration and hemodynamic changes [13]. Bizarro and AUSTIN’s research have similar results, with VA ECMO having a higher incidence of nosocomial infections than VV ECMO [10, 37]. Possible reason is related to wound infection at the site of arterial catheterization in VA ECMO patients [10]. However, some studies have found that VV ECMO mode has a higher likelihood of VAP occurrence, which may be due to patients receiving VV ECMO receiving longer ECMO treatment and mechanical ventilation time [26]. Heart transplantation and immunosuppression are risk factors for nosocomial infection in ECMO patients. Heart transplantation is an effective method to treat end-stage heart disease. However, due to preoperative heart failure, it is often accompanied by multiple organ dysfunction. After a long period of general anesthesia, extracorporeal circulation and other invasive operations, steroids and other Immunosuppressive drug after transplantation may affect wound healing and increase the risk of infection. Therefore, medical staff should do a good job in monitoring the nosocomial infection of ECMO patients after Heart transplantation, which is conducive to the timely detection, diagnosis, treatment and supervision of nosocomial infection.

Blood transfusion products contain various immune neurotransmitters, such as residual white blood cells, aged red blood cells, residual platelets, etc. These immune neurotransmitters can promote the release of anti-inflammatory cytokines, leading to a decrease in neutrophil and natural killer cell activity, inducing immune suppression and increasing the risk of nosocomial infections in patients, which has a negative impact on the prognosis of critically ill patients [3840]. In recent years, some studies have recommended restrictive transfusion strategies, which patients can benefit from. Implementing restrictive blood transfusion strategies may potentially reduce the incidence of nosocomial infections. Studies have shown that starting blood transfusions in ECMO patients with Hb<7 g/dL did not lead to an increase in patient mortality [4042].

This review provides a reference for the prevention of nosocomial infections in patients treated with ECMO. In clinical work, medical staff should identify high-risk groups of ECMO nosocomial infections, actively take preventive measures, and reduce the incidence and mortality of nosocomial infections. At the same time, in the future research, more high-quality multi center prospective Cohort study is needed to evaluate the risk factors of nosocomial infection in ECMO patients more scientifically and comprehensively, so as to provide reliable basis for the prevention of nosocomial infection in ECMO patients. It is undeniable that this study has some limitations. Firstly, the baseline differences among the included subjects are significant, and the risk factors interact with each other. However, due to the limited number of included studies, detailed subgroup analysis cannot be conducted, which may affect the effectiveness of statistical analysis. Secondly, it is not possible to calculate the estimated effects of all risk factors, as only two or more studies related to nosocomial infection risk factors with the same definition were summarized in the meta-analysis. Finally, the quality of the included literature varies, with some studies having small sample sizes, which affects the accuracy of the results and may limit the universality of the research results. However, our research results have made an important contribution to determining the risk factors of nosocomial infection in ECMO patients by integrating studies involving ECMO nosocomial infection risk factors.

Conclusion

In summary, this study shows that immunosuppression, heart transplantation, VA-ECMO, ECMO support time, mechanical ventilation time, CRRT, red blood cell input, ICU hospitalization time, and total hospitalization time are risk factors for nosocomial infections in ECMO treated patients. In clinical work, medical staff should identify high-risk populations for ECMO nosocomial infection, actively take preventive measures, and reduce the incidence and mortality rate of nosocomial infection. Due to the limitations of inclusion in the research institute, the above conclusions still need to be further validated through large-scale, high-quality prospective cohort studies.

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