Bacteremia and Mortality among Patients with Nontunneled and Tunneled Catheters for Hemodialysis

Introduction Central venous catheters for hemodialysis (HD) can be nontunneled catheters (NTC) or tunneled catheters (TC). Bacteremia and dysfunction are complications that can impact morbidity and mortality. We decided to compare the rates of bacteremia and dysfunction between NTC and TC and patient survival 90 days after catheter insertion. Methods Retrospective cohort to evaluate catheters inserted between January 2011 and December 2020 in a tertiary hospital. Catheters in patients with end-stage chronic kidney disease were included. Patients with acute kidney injury, catheters that lasted less than three HD sessions, and patients who died within one week after insertion were excluded. Bacteremia and dysfunction rates, bacteremia-free survival, and dysfunction-free survival were investigated. Multivariable analysis was performed using a Cox proportional hazards regression model for patient survival at 90 days. Results 670 catheters were analyzed in 287 patients, 422 NTC (63%), and 248 TC (37%). The rates of confirmed bacteremia per 1,000 catheter-days were 1.19 for NTC and 0.20 for TC (p < 0.0001). The confirmed or possible bacteremia rates were 2.27 and 0.37 per 1,000 catheter-days for NTC and TC, respectively (p < 0.0001). The dysfunction rates were 3.96 and 0.86 for NTC and TC, respectively (p < 0.0001). Patient survival at 90 days was higher in the TC group than the NTC group (96.8% vs. 89.1%; p < 0.0001). Conclusion We found lower rates of bacteremia and dysfunction for TC and demonstrated that using NTC affects patient mortality.


Introduction
Chronic kidney disease (CKD) is a clinical syndrome based on the presence of kidney damage or reduced kidney function (glomerular fltration rate (GFR) < 60 ml/min/ 1.73 m 2 ) for three months or more [1].When GFR is less than 15 ml/min/1.73m 2 , kidney function is not capable of maintaining life for a long time [2], and renal replacement therapy (RRT) such as hemodialysis (HD) or kidney transplantation is necessary to prolong life and reverse uremic symptoms [3].For HD to be performed, patients must have vascular access for hemodialysis.Central venous catheters (CVC) are indicated in cases of emergency hemodialysis or, in chronic hemodialysis, in cases where it is not possible to perform an arteriovenous fstula [4] or where it is dysfunctional [5].
Tunneled cufed catheters for hemodialysis were developed as a technological breakthrough to anchorage it subcutaneously and to reduce infections as used in other circumstances, such as peritoneal dialysis, chemotherapy, and parenteral nutrition.In Brazil, according to the Brazilian Dialysis Census, 23.6% of patients with hemodialysis (HD) use central venous catheters (catheters), 9.2% of nontunneled catheters (NTC), and 14.4% of tunneled catheters (TC) [6].Te use of a catheter for HD access is associated with an increase in all-cause mortality compared to the use of arteriovenous fstula (AVF) [7], and some complications may be related to the presence of a catheter, including infections [5] and dysfunction [8].Catheter-related infections are responsible for signifcant rates of hospitalization and mortality [9], especially those that progress to bacteremia [10], while dysfunction can imply a reduction in HD efectiveness [8].Interestingly, previous studies report that TC has lower bacteremia rates than NTC [11,12].
Despite continuing progress in hemodialysis therapy, the mortality rate is unacceptably high in catheter patients [13].In addition, other factors are associated with the high prevalence of mortality, especially cardiovascular disease [14], anemia, infammation, hypoalbuminemia [15], and low-dose hemodialysis, quantifed by Kt/V [16].
Furthermore, we evaluated bacteremia and dysfunction rates for NTC and TC in a large single-center retrospective cohort and risk factors for 90-day survival in patients who used catheters as vascular access to HD.

Methodology
2.1.Study Design.Tis retrospective cohort study evaluated catheters inserted in end-stage renal disease patients from January 1, 2011, to December 31, 2020, in a tertiary hospital in Northeast Brazil.Patients undergoing hemodialysis due to acute kidney injury, catheters lasting less than 3 (three) hemodialysis sessions, death within one week after insertion, or transfer to another hemodialysis service within one week after hemodialysis catheter insertion were excluded.Te NTCs were inserted by a nephrologist in a specifc room for minor surgical procedures, without ultrasound-guided, while the TCs were inserted by a vascular surgeon guided by fuoroscopy.Te catheter insertion site and the catheter model were defned by the physician who would perform the implant.Te nontunneled catheter model used was Arrow ® (Telefex).Tunneled catheter models were Split Cath ® (Medcomp), Palindrome ™ (Medtronic), and Equistream ™ (BD).All patients were in conventional 4-hour hemodialysis sessions with low-fux dialyzers.Blood fow rates were prescribed individually to reach a single-pool Kt/V of 1.3.In all dialysis sessions, the exit site and the subcutaneous tunnel were evaluated by the nursing team according to the institution protocol, and the dressing material was changed with sterile gauze after cleaning with 2% alcoholic chlorhexidine.Te study was approved by the local Medical Ethics Committee (No. 5,079,821, of November 4, 2021).

Data Collection.
All medical data were collected from the electronic medical record.Clinical and laboratory data such as age, diagnosis of diabetes mellitus, serum levels of hemoglobin, and albumin were collected at catheter insertion.Te Kt/V was calculated after catheter insertion.All information about the catheter was also included: type of catheter used (nontunneled or tunneled), insertion site, catheter survival, reasons for catheter removal, and occurrence of death.All catheters were followed from the time of insertion until removal.

Defnitions and Outcomes.
Catheter-related bacteremia was diagnosed as confrmed or possible confrmed as follows: Confrmed bacteremia was defned as the presence of the same organism from a semiquantitative culture of the catheter tip and from a peripheral or catheter blood sample in a symptomatic patient with no other apparent source of infection [17].
Possible bacteremia was defned as the presence of symptoms related to bacteremia that occurred without signs and symptoms of infection related to other sites and with negative cultures (blood culture or catheter tip culture) but with clinical improvement and defervescence with catheter removal and the initiation of antibiotic therapy [17].
Although the exit site and tunnel infection were not part of the primary outcome, these outcomes were evaluated and diagnosed according to the KDOQI criteria [8].If patients with exit site or tunnel infection had systemic symptoms, they were characterized as bacteremia.Following the institutional protocol for possible catheterrelated bacteremia, two blood samples (peripheral, from the hemodialysis circuit or catheter) were collected in blood culture bottles (Bactec 9240, Becton Dickinson).Until 2018, catheter-tip segment cultures were performed.All catheters with possible or confrmed infection are routinely removed at the institution.
Catheter dysfunction was confrmed when the catheter did not provide blood fow greater than 200 ml/min for more than 2 (two) hemodialysis sessions.Te catheter was removed, and a new catheter was inserted.
Te primary outcome was to assess the rates of possible and confrmed bacteremia per 1,000 catheter-days and bacteremia-free survival among nontunneled and tunneled catheters.Te dysfunction rate and dysfunction-free survival were also analyzed.Catheters with bacteremia and dysfunction simultaneously were defned as catheter-related bacteremia.
Te secondary outcome was to analyze patient survival in the frst 90 days of catheter use.Variables such as age, diabetes mellitus, type of catheter, insertion site, bacteremia, dysfunction, hemoglobin, albumin, and Kt/V were included as predictors.

Statistical Analysis. Statistical analysis was performed using the IBM SPSS
® version 20.0 program.Data were presented using the mean ± standard deviation, median (1 st and 3 rd quartiles), and percentage rates.Normally distributed variables were compared using Student's t-test, and nonnormally distributed variables were compared using the Mann-Whitney U test.Te chi-square test was used to compare categorical variables.Bacteremia and dysfunction rates (events per 1,000 catheter-days) were compared using the log-rank test.Te Kaplan-Meier method and the logrank test were used to analyze bacteremia-free and dysfunction-free survival.All patients were censored in the survival analysis if the arteriovenous access was mature, if they were transferred to peritoneal dialysis, if they underwent kidney transplantation, or if they were lost to follow-up.For the analysis of patient survival at 90 days, an unadjusted and adjusted analysis was performed using the Cox proportional hazards regression model and presented as the hazard ratio (HR) and 95% confdence intervals (95% CI).For adjusted analysis, we included age, diabetes, catheter type, vein location, presence of confrmed bacteremia and dysfunction, hemoglobin, and albumin.Te p value was considered signifcant at p < 0.05.

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International Journal of Nephrology

Bacteriological Profle.
Te microbiological profle of cultures with bacteremia is shown in Table 3.

Discussion
Central venous catheters are often used as vascular access for hemodialysis.However, device infection is one of the most severe complications [18].Similarly, catheter dysfunction is a common complication associated with reduced adequacy, increased risk of catheter-related bloodstream infection, and mortality [8].Tis study demonstrated higher bacteremia rates and dysfunction in nontunneled catheters for outpatient hemodialysis.[22].A previous study in Singapore, a country with a tropical climate similar to Brazil, revealed a bacteremia rate in tunneled HD catheters of 0.75 per 1,000 catheter-days [23].In our cohort, the incidence of bacteremia (possible or confrmed) was 2.27 per 1,000 catheter-days for nontunneled catheters and 0.37 per 1,000 catheter-days for tunneled catheters.
Tere is variability between catheter-related bacteremia rates for HD in previous studies.Te bacteremia rates found in our study were low for nontunneled and tunneled catheters.A possible explanation for the reduced rates of catheter-associated infection was the follow-up of protocols and care by the nursing team throughout the hemodialysis session, which includes the use of 2% chlorhexidine to clean the exit site of the catheter, in addition to a continuing education program on the prevention of catheter complications.Previous studies have shown reduced bacteremia in patients after establishing a catheter care procedure using 2% chlorhexidine [24].Furthermore, continuing education for patients and their families and an easy access route for patients and healthcare professionals to get help with catheter problems is the key to maintaining low bacteremia rates [23].
A previous study reported that coagulase-negative Staphylococcus aureus was the pathogen most commonly isolated in nontunneled catheter infections [25].Similarly, another study noted that Gram-positive microorganisms were responsible for most cases of tunneled catheter infection, and 40 to 81% of infections were caused by Staphylococcus aureus [26].An Indian study indicated high bacteremia rates in tunneled catheter patients (42% at 180 days) with a higher incidence of Gram-negative bacteria growth in blood cultures.Tis fnding was attributed to the low socioeconomic status of patients, poor hygiene, and water contamination in the HD service [27].In our study, International Journal of Nephrology episodes of Staphylococcus aureus bacteremia were predominant only in nontunneled catheters.Tis may be due to the small number of confrmed bacteremia in tunneled catheters.
Regarding dysfunction, a previous study found an overall incidence rate of catheter dysfunction of 10.58 per 1,000 catheter-days, 12.86 per 1,000 catheter-days for nontunneled catheters, and 8.64 per 1,000 catheter-days for   4 International Journal of Nephrology tunneled catheters [28].Our study found a rate of 3.96 per 1,000 catheter-days for nontunneled catheters and 0.86 per 1,000 catheter-days for tunneled catheters.Te low rate of dysfunction reported in our study can be explained by the fact that we used as a dysfunction criterion the catheter that does not provide blood fow greater than 200 ml/min.According to Grifths et al., blood fow rates less than 300 ml/min are often used to defne hemodialysis catheter dysfunction [8,29].HD patients with catheters are associated with hypoalbuminemia compared to patients using AVF as vascular access.Tis association is multifactorial, and one of the causes is infection and poor dialysis adequacy [30,31].Among the characteristics of the patients analyzed, serum albumin levels and Kt/V showed a diference between patients with nontunneled and tunneled catheters, which was higher in patients with tunneled catheters.Te catheter survival time was higher for TC with statistical signifcance.A study reported a median catheter survival of 62.5 days for TC [32].In our cohort, the median duration of TC was 185 days.Tere was a diference in bacteremia and dysfunction-free survival, which was more signifcant in tunneled catheters.Tese fndings refect the lower rates of bacteremia and dysfunction in these catheters, with a lower need for removal.
Regarding patient survival 90 days after catheter insertion, there was an additional mortality risk of 3% for each year of patient life.In fact, in a Korean study, elderly patients with catheters as vascular access for HD had higher mortality than those with AVF [33].An inverse relationship between serum levels and mortality risk has been demonstrated about albumin.Previous studies have shown that in hemodialysis patients, hypoalbuminemia is a risk factor for death [34].Furthermore, in our study, the mortality risk was also higher in individuals with nontunneled catheters than those with tunneled catheters.A study in Palestine that compared mortality in patients with AVF and catheter as vascular access for HD also reported higher mortality in the catheter group.In this study, most devices in the catheter group were nontunneled catheters [35].A similar result was found in a study in Sarajevo, International Journal of Nephrology which revealed an increase in mortality rates in patients using nontunneled catheters compared to patients using AVF or tunneled catheters [36].
While other studies have linked bacteremia to increased mortality in hemodialysis patients, our study's multivariable regression model did not fnd it to be a signifcant risk factor.Tis may be due to the low occurrence of confrmed bacteremia and the fact that confrmed bacteremia and dysfunction frequently occurred after 90 days for both catheter types (26.1% for bacteremia and 25.5% for dysfunction).However, our study found that a nontunneled catheter predicted poor survival, even without a relationship with bacteremia, in our regression model.Lower serum albumin levels and lower HD adequacy for nontunneled catheter patients may explain this [37].
Our study has some limitations.Firstly, this is a retrospective analysis.Terefore, there is a lack of information, including causes of death, cardiovascular diseases, or other risk factors that impact patient mortality, such as serum phosphorus levels, potassium, infammatory markers, and blood volume status.Secondly, as the data were collected from medical records, there may have been underreporting of outcomes, which could explain the low incidence of bacteremia and dysfunction.Another signifcant limitation is the lack of information about catheter type indication.Probably, the indication by the nephrology team of which catheter type should be inserted was decided based on the vascular surgeon and device availability.
In conclusion, tunneled catheters had lower rates of bacteremia and dysfunction than nontunneled catheters.Additionally, nontunneled catheters infuenced mortality in the frst 90 days after insertion compared to tunneled catheters.According to this study, it is recommended to choose tunneled catheters instead of nontunneled ones for patients undergoing chronic HD treatment.It is wise to consider switching to a tunneled catheter while waiting for an arteriovenous fstula or arteriovenous graft.However, as this is a retrospective study, further studies are needed.
Dysfunction.A total of 92,008 days were analyzed (27,751 days for NTC and 64,257 days for TC).
Sahli et al. demonstrated in a study with nontunneled catheters in outpatients an infection rate of 16.6 per 1,000 catheter-days, with a catheter-related bacteremia rate of 10.8 per 1,000 catheter-days [19].Moran et al. found a bacteremia rate of 0.91 per 1,000 catheter-days [20], while Maki et al. (2011) documented a bacteremia rate of 0.82 per 1,000 catheter-days [21] for tunneled catheters.Martin et al. found a confrmed or possible bacteremia rate for tunneled hemodialysis catheters of 1.28 per 1,000 catheter-days

Table 1 :
Clinical and laboratory characteristics of patients and catheters.

Table 2 :
Event rates between nontunneled and tunneled catheters.

Table 4 :
Cox proportional hazards regression model for 90-day survival.