Risk Factors for Catheter-Related Bloodstream Infection in Patients Undergoing Hemodialysis: A Systematic Review And Meta-Analysis

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Risk Factors for Catheter-Related Bloodstream Infection in Patients Undergoing Hemodialysis: A Systematic Review And Meta-Analysis

https://doi.org/10.21203/rs.3.rs-1970692/v1

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Background: Catheter-Related Bloodstream Infection (CRBSI) is a common and life-threatening complication of hemodialysis, with high morbidity and mortality. This meta-analysis was performed to analyze the risk factors of CRBSI in patients undergoing hemodialysis.

Methods: The search process included the electronic databases of CNKI, WANGFANG, PubMed, EMBASE, the Cochrane Library, and Web of Science from inception to July 2021. The quality assessment of the included studies was conducted according to the Newcastle-Ottawa Scale (NOS). The Odds ratios (ORs) with corresponding 95% confidence intervals (95%CIs) were calculated to assess the strength of the association of risk factors with CRBSI using RevMan 5.4 software in the current study.

Results: A total of 23 pieces of literature were included in this study, counting a total of 10335 patients, including 1165 patients with CRBSI and 9170 patients without CRBSI. Meta analysis results showed that puncture times [OR=3.22, 95% CI (2.42, 4.27)], femoral vein catheterization (OR=1.69, 95%CI 1.38-2.08, P＜0.00001), catheter indwelling time (OR = 2.22, 95% CI 1.62-3.04, P < 0.0001), age (OR =1.69, 95%CI 1.49-1.91, P < 0.0001), diabetes mellitus (OR=1.92, 95%CI 1.71-2.15, P< 0.00001), dialysis time (OR = 2.89, 95%CI 1.82-4.59, P <0.0001), duration of hospitalization (OR =2.49, 95%CI 1.47-4.23,P =0.0006) and hypoproteinemia (OR =3.19, 95%CI 2.08-4.89, P＜0.0001) were risk factors for CRBSI.Conclusions: Catheter retention time, age, femoral vein catheterization, diabetes, hospitalization time and hypoproteinemia were risk factors for CRBSI in hemodialysis patients.

Catheter-Related Bloodstream Infection

Risk factors

Hemodialysis (HD) is mainly used in end-stage renal disease, drug poisoning, acute kidney injury, refractory heart failure, pulmonary edema, hepatorenal syndrome, and other conditions. It is an essential means of renal replacement therapy for patients with acute and chronic renal failure, effectively improving the symptoms and reducing the mortality of renal failure patients^[1–2]. Catheter-related bloodstream infections (CRBSI), central venous stenosis, electrolyte disturbance, and other complications often occur during hemodialysis^[3–4]. CRBSI is a common complication of hemodialysis. Patients with CRBSI typically require a more extended hospital stay, raising medical costs and risking their lives ^[5–8]. According to the investigation and study by the Centers for Disease Control and prevention of the United States ^[9], the average infection rate of CRBSI in the United States is 5.3/1000 indwelling catheter days, and the average mortality rate of infected patients can be as high as 25%. Therefore, it is urgent to find out the risk factors of CRBSI to reduce its incidence. There are various reports on the risk factors of central venous CRBSI in hemodialysis patients. Age, diabetes, catheter placement time, and catheter position have been reported as risk factors for central venous CRBSI in hemodialysis patients ^{[10–12.47−48]}. Martin and Caylan's research pointed out that the risk factors of central venous CRBSI in hemodialysis patients include the catheterization site, hand hygiene, use of antibiotics, and emergency catheterization ^[49–50]. It is critical to understand the factors contributing to the occurrence of CRBSI, minimize the risk of infection, and alleviate the economic burden on patients. This study conducted a systematic review and meta-analysis on the risk factors of CRBSI to summarize the risk factors CRBSI and provide clinical guidance.

This study was designed and performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines^[13].

Data sources and searches

The following electronic databases were searched: CNKI, WanFang Data, PubMed, EMBASE, The Cochrane Library, and Web of Science from inception to July 2021.The search terms included “hemodialysis” or “maintenance hemodialysis” or “hemodialysis” or” dialyzes” and “catheter-related infection” or “catheter-associated infections” and “risk factor” or “relevant factor” or “influencing factor” or “risk score.” The references from the included studies and recent reviews were also searched.

Selction criteria

Inclusion criteria: (1) Observational studies, cross-sectional studies, cohort studies, or case-control studies were included; (2) The subjects were patients who needed hemodialysis, with a length of stay of more than 24 hours; (3) The study results included CRBSI risk factor data reported with 95% confidence interval (95% CI) or odds ratio (or); (4) The diagnostic criteria of CRBSI were met.

Exclusion criteria: (1) Duplicate studies; (2) Incomplete studies;(3) No outcome indicator or odds ratio (OR).

Data extraction

The data from all eligible studies were independently extracted by two authors (LYH and YL). The following variables were extracted from each study: first author’s name, publication year, country, study design, sample size, age, sex ratio, study quality score. Any disagreement was resolved by discussion or consultation from a senior reviewer to reach a consensus.

Quality assessment

As previously described, two reviewers (YL and LYH) independently assessed the quality of all included studies according to the Newcastle-Ottawa Scale (NOS) ^[14]. A total of three items were evaluated: patient selection, comparability of the two study arms, and assessment of the outcomes. The studies were classified according to their quality: high quality (7-9 points), moderate quality (5-6 points), poor quality (0-4 points).

Data synthesis and analysis

Review Manager (Rev Man version 5.4) was used to perform all the statistical analyses. The pooled ORs with corresponding 95% Cis of risk factors were calculated to assess their association with CRBSI. The heterogeneity between studies was evaluated based on the Q-test and I2 statistics. When there was no statistically significant heterogeneity across studies (I2＜50%, P＞0.05, a fixed‐effects model was used to calculate pooled effects. Otherwise, a random-effects model was adopted. If the synthesis was inappropriate, the results were presented descriptively. Multiple sensitivity analyses were conducted to explore the potential heterogeneity between studies and the possible causes of heterogeneity. Studies with a potential risk of bias were removed, and the pooled estimates were compared with and without the drawn studies. The publication bias was assessed using a funnel plot.

Study selection and baseline characteristics

A total of 789 relevant pieces of literature were retrieved, including 483 in English and 306 in Chinese. After the removal of 293 duplicate articles, 496 articles remained. After reading the title and abstract, 339 articles were excluded, leaving 157. Subsequently, the investigators read the full texts and excluded 134 studies. Finally, 23 pieces of literature were included in the current study [10-12,16-35]. A total of 10335 individuals were enrolled, including 1165 with CRBSI and 9170 without CRBSI. The literature screening process is presented in Figure 1.

The clinical characteristics of the included studies are presented in Table 1. Twenty-four studies were included in the meta-analysis. These studies reported the association between CRBSI occurrence and various factors: seven studies reported the puncture times, four studies reported femoral vein catheterization, fifteen studies described the catheter indwelling time, twelve studies investigated the age, fifteen studies reported diabetes, three studies examined the dialysis time, three studies reported the length of hospital stay and four studies reported hypoproteinemia. Twenty studies originated from China, one was derived from the USA, one was completed in Turkey, one study was from France, and one study was carried out in Iran.

Table 1 Basic characteristics of the included studies

Author	Country	Design	Age	Number (M/F)	CRBSI (Yes/No)	Risk factors	NOS score
Ding 2020	China	Prospective cohort	49.72±2.18	NA	NA	Age; Dialysis time;	8
Jiang 2016	China	retrospective case-control	57.50±11.30	60(38/22)	60/1270	Catheter indwelling time;	6
Liu 2020	China	retrospective case-control	61.4±3.1	12(5/7)	12/58	Age; Diabetes; Length of hospital stay;	7
Chen 2020	China	retrospective case-control	58.64±10.40	57(32/25)	57/341	Puncture times; Catheter indwelling time; Age; Diabetes; Length of hospital stay; Hypoalbuminemia	7
Shi 2021	China	retrospective case-control	NA	32(18/14)	32/74	Catheter indwelling time; Age; Diabetes; Length of hospital stay	7
Zhang 2021	China	retrospective case-control	62.7±5.1	23(14/9)	23/177	Puncture times; Femoral vein catheterization; Age; Diabetes; Catheter indwelling time	6
Zhang 2021	China	prospective cohort	53.72±12.0	35(21/14)	35/180	Catheter indwelling time; Age;	7
Wan 2014	China	retrospective case-control	57.2±16.3	NA	34/330	Diabetes	8
Wang 2021	China	retrospective case-control	58.4±16.2	80(44/36)	80/750	Puncture times; Age; Diabetes	7
Li 2019	China	retrospective case-control	NA	70(40/30)	70/365	Puncture times; Femoral vein catheterization; Catheter indwelling time; Diabetes; Hypoproteinemia	7
Wang 2020	China	retrospective case-control	NA	60(40/20)	60/260	Catheter indwelling time; Dialysis time;	6
Shen 2020	China	retrospective case-control	NA	24(14/10)	24/1974	Catheter indwelling time; Age; Diabetes	6
Cao 2019	China	retrospective case-control	NA	78(36/42)	78/263	Diabetes; Hypoalbuminemia	7
Li 2018	China	prospective cohort	52.77±6.52	35(22/13)	35/45	Puncture times; Catheter indwelling time; Diabetes;	7
Lv 2021	China	prospective cohort	58.62±8.73	31(19/12)	32/66	Femoral vein catheterization; Hypoalbuminemia	7
Hua 2019	China	retrospective case-control	70.18±8.4	31(14/17)	31/125	Femoral vein catheterization; Age; Dialysis time	7
Chen 2019	China	prospective cohort	66.41±11.04	18(7/11)	18/81	Catheter indwelling time; Age; Diabetes	7
Samani 2014	Iran	Rcross-sectional	58.5±12	44(23/21)	44/176	Puncture times; Catheter indwelling time;	7
Martin 2020	USA	prospective cohort	NA	39(23/16)	39/188	Catheter indwelling time; Diabetes	7
Caylan 2010	Turkey	prospective cohort	NA	63(34/29)	63/185	Puncture times	8
Lemaire 2009	France	retrospective cohort study	NA	226(102/124)	226/1523	Catheter indwelling time; Diabetes	7
Li 2021	China	retrospective case-control	NA	36(25/11)	36/340	Catheter indwelling time; Age; Diabetes	6
Sun 2018	China	retrospective case-control	53.72±12.03	35(21/14)	35/180	Age; Diabetes; Catheter indwelling time;	6

Results of meta-analysis

The risk factors associated with CRBSI were integrated into the current study. The results showed that 9 factors, including puncture times, femoral vein catheterization, catheter indwelling time, age, diabetes, dialysis time, hypoproteinemia and hospitalization time were associated with CRBSI.

Puncture times

The relationship between puncture time and CRBSI was reported in seven studies. Significant heterogeneity was observed between studies, and sensitivity analysis was performed. Two articles were removed, and data were synthesized using a fixed-effects model (I² = 0%, P＜0.52). The pooled results indicated that puncture times were a risk factor for CRBSI (OR=3.22, 95%CI 2.42-4.27, P＜0.00001)(Figure 2).

Femoral vein catheterization

Four studies reported the relationship between femoral vein catheterization and CRBSI. No significant heterogeneity was observed across studies, so a fixed-effects model was used to conduct the data synthesis (I² = 38%, P = 0.18). The pooled results identified femoral vein catheterization as a risk factor for the occurrence of CRBSI (OR = 1.69, 95% CI 1.38-2.08, P < 0.0001) (Figure 3).

Catheter indwelling time

The relationship between catheter indwelling time and CRBSI was described in 14 studies. Since the research results demonstrated significant heterogeneity (I²= 83%, P < 0.00001), a random-effects model was adopted to conduct the data synthesis. The pooled results indicated that catheter indwelling time is a risk factor for the occurrence of CRBSI (OR = 2.22, 95% CI 1.62-3.04, P＜0.0001) (Figure 4). To identify the potential source of heterogeneity, we conducted a sensitivity analysis. No change in the results was noted after excluding each study, indicating that the results were stable. Subsequently, we conducted a subgroup analysis according to the type of study, revealing that catheter indwelling time is a risk factor for the occurrence of CRBSI in the retrospective case-control group (OR=1.59, 95%CI=1.41,1.80) and other study type groups (OR=1.72, 95%CI=1.54,1.93).

Age

Twelve studies reported the relationship between age and CRBSI. Significant heterogeneity was observed between studies, and sensitivity analysis was performed. Two articles were removed, and data were synthesized using a fixed-effects model (I² = 47%, P =0.04).The pooled results indicated that age is a risk factor for the occurrence of CRBSI (OR = 1.69, 95% CI 1.49-1.91; P＜0.00001) (Figure 5).

Diabetes

Fifteen studies reported the relationship between diabetes and CRBSI. No significant heterogeneity was observed across studies. Therefore, a fixed-effects model was used to conduct the data synthesis (I²= 23%, P = 0.21). The pooled results demonstrated that diabetes is a risk factor for the occurrence of CRBSI (OR = 1.92, 95% CI 1.71-2.15, P＜0.00001) (Figure 6).

Dialysis time

Three studies reported the relationship between dialysis time and CRBSI. There was no significant heterogeneity across studies, and a fixed-effects model was used to conduct the data synthesis (I²= 0%, P = 0.74). The pooled results indicated that dialysis time is a risk factor for the occurrence of CRBSI (OR = 2.89, 95%CI 1.82-4.59, P < 0.00001) (Figure 7).

Length of hospital stay

The relationship between the length of hospital stay and the occurrence of CRBSI was described in three studies. No significant heterogeneity was observed across studies, so a fixed-effects model was used to conduct the data synthesis (I² = 39%, P = 0.19). The pooled results indicated that the length of hospital stay is a risk factor for the occurrence of CRBSI (OR = 2.49, 95%CI 1.47-4.23; P = 0.0007) (Figure 8).

Hypoproteinemia

Four studies reported the relationship between hypoproteinemia and CRBSI. Significant heterogeneity was observed between studies (I²=58%, P =0.07). Therefore, sensitivity analysis was conducted, revealing that Chen's study^[19]was the main source of heterogeneity. After eliminating this study, the data were synthesized using a fixed-effects model (I² = 0%, P =0.79). The pooled results indicated that hypoproteinemia is a risk factor for the occurrence of CRBSI (OR = 3.19, 95%CI 2.08-4.89; P＜0.000001) (Figure 9).

Publication bias

A funnel plot was applied to assess publication bias. In the current study, only the diabetes risk factor was assessed for publication bias. Overall, the results showed a roughly symmetrical figure, indicating no publication bias. (Figure 10).

The study found that CRBSI was associated with age, diabetes, and hypoproteinemia. Our results demonstrated that diabetic patients were 1.92 times more likely to develop CRBSI. Moreover, foreign scholars reported that diabetes mellitus increased the risk of CRBSI by 60% ^[36]. The current research shows that a long-term hyperglycemic state results in increased blood viscosity, faster protein breakdown, reduced synthesis, reduced immunoglobulin and antibodies, and abnormal cytokine secretion, causing decreased immunity and promoting the occurrence of CRBSI ^[37]. In addition, the hyperglycemic environment is conducive to bacterial reproduction, enhances the virulence of bacteria, and further induces infection ^[38]. This study revealed that patients with hypoproteinemia are prone to CRBSI, and patients with hemodialysis often have protein loss. Patients with low protein levels may have impaired neutrophil, and macrophage function, inhibited T lymphocyte differentiation, and lower total number and activity of cells. These changes result in decreased immunity, thus increasing the risk of infection ^[39].

In addition, this study shows that age also increases the risk of CRBSI. Elderly patients on hemodialysis have impaired immune function as they often suffer from diabetes and hypoalbuminemia and may develop CRBSI. For uremic patients on hemodialysis, toxin accumulation is frequently accompanied by pulmonary edema, pulmonary interstitial fibrosis, thick respiratory secretions, and alveolar fibrin exudates, leading to the growth of pathogenic bacteria. The incidence of CRBSI in these patients is significantly increased due to their decreased immunity ^[40].

The analysis of the included studies revealed that the catheter-related factors of CRBSI had catheter frequency, femoral vein catheter, dialysis time, and catheter indwelling time. This study shows that the number of catheterizations can affect the occurrence of CRBSI in hemodialysis patients. Multiple punctures may cause not only damage to the vascular wall but also affect the skin around the catheter, which may lead to the migration and reproduction of bacteria along the surface of the catheter. Bacteria adhere to the catheter surface and are continuously released into the blood, causing CRBSI ^[41]. The study found that the risk of CRBSI in patients with femoral vein catheterization was higher than in other locations. Given the proximity of the femoral vein catheterization site to the perineum, it is prone to contamination by feces and urine ^[42].

Furthermore, the skin in the groin area is wrinkled and moist, which is conducive to bacterial reproduction, leading to infection. In addition, some researchers pointed out that ^[27] patients with decreased lower limb blood flow often required multiple hemodialysis sessions to complete the treatment, which increased the probability of bacterial invasion from the catheter. As the right internal jugular vein lies in a straight line with the right atrium and superior vena cava and has unobstructed blood flow, it is recommended to catheterize hemodialysis patients in the right internal jugular vein ^[43].

This study revealed that dialysis time could also affect the occurrence of CRBSI. The extended dialysis duration results in a more prolonged catheter exposure to the air. Thus, patients remain in an environment with pathogenic microorganisms, increasing the risk of CRBSI ^[44]. Moreover, studies have found that extended indwelling catheter times were associated with higher infection rates ^[45]. A long-term indwelling catheter causes severe damage to the vascular endothelium, leading to phlebitis. Furthermore, a fibrin sheath may develop on the surface of the catheter. After the puncture, bacteria may migrate along the surface of the catheter, causing CRBSI ^[46].

Patients with extended hospital stays are at a higher risk of CRBSI. Considering that patients with prolonged hospital stays may have a more severe and complex conditions, they may have impaired immune functions. Patients with extreme conditions are more likely to have anemia, and hypoproteinemia, thus increasing the risk of CRBSI in hemodialysis patients. In some pieces of literature, it was reported that using immunosuppressants ^[18], the catheter type ^[25], hospital environment ^[32], hypertension ^[34], and other risk factors increased the risk of CRBSI. However, the results could not be summarized due to the small amount of literature.

Due to the small number of risk factors and included studies in this analysis, a funnel chart cannot be drawn, and publication bias may be present. (2) The reliability of the meta-analysis results is affected by the quality and source of the literature. This study only searched the published literature but not the literature in the unpublished studies. (3) There was heterogeneity among the included studies, and the results of individual indicators were not robust, affecting the credibility of the results to a certain extent. In conclusion, the above three limitations have different effects on the outcome, so the meta-analysis results still need further verification.

Identifying the risk factors of CRBSI is an essential prerequisite for preventing and controlling infection in hemodialysis patients. The meta-analysis indicated that age, indwelling catheter time, hypoproteinemia, and femoral vein catheterization were independent risk factors for the occurrence of CRBSI. Future studies should focus on investigating the relationship between risk factors and CRBSI in hemodialysis patients.

Data availability

All data generated or analysed during this study are included in this published article.

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No competing interests reported.

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