Survival of Tunneled Double Lumen-Cuffed Catheters in Children on Maintenance Hemodialysis – A Retrospective Cohort Study

Introduction

Despite strong recommendations of fistula first, tunneled cuffed catheters (TCC) remains the commonest vascular access used globally for maintenance hemodialysis (HD) in children.[1] Boryzch-Duzalka et al.[2] consolidated data from 27 European countries performing HD in children and found that despite a gradual increase in the creation of arterio-venous fistula (AVF), 90% of children below 10 years of age still continued to have TCC as access for HD. In the US, almost 80% of children continue to be dialyzed through a TCC.[34] Catheter-related blood stream infections (CRBSIs) have been an important cause of premature catheter removal, increased morbidity, hospitalization, and death rates.[5678] Catheter malfunction due to thrombus, malposition, or kink are the other major reasons for catheter failure.[9101112]

Creation of AVF in pediatric population has a major challenge in the narrow caliber vessels which requires expert personnel. Owing to this, the use of TCCs for HD is as high as 87–89% in few developing nations.[2] Reports from single center studies show a heterogeneous outcome with some reporting catheter survival rates in middle and low-income countries to be comparable to those in high-income countries, while others have reported higher rates of CRBSI or shorter catheter survival rates.[91314]

In India, there has been a slow but steady increase in the number of centers offering maintenance HD for children in the last 10–12 years. Outcome studies are scarce and have shown a high mortality and dropout rates.[1516] Despite the wide use of tunneled catheters, the incidence of catheter-related complications and the catheter survival rates are not known.

This study was undertaken to determine the infection free survival rate of TCCs, the incidence and causes of catheter failure, and the associated risk factors in children undergoing maintenance HD through tunneled catheters at our pediatric dialysis center in a public hospital serving children from a low socioeconomic background.

Methodology

This was a retrospective cohort study conducted at the pediatric nephrology division of a tertiary care children’s hospital in Mumbai. The study was conducted over a 6-year period from September 1, 2012 to September 30, 2018. Subjects included all children who had a TCC inserted at our hospital for maintenance HD and received treatment for >3 months. Patients were selected consecutively by the complete enumeration sampling technique from the dialysis records. Children who opted for dialysis treatment at a different center within 3 months of catheter insertion were excluded from the study [Figure 1].

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Figure 1

Flow chart explaining the data collection

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Data was collected from the medical records, from the time of catheter insertion until the time of removal, or in case of persistent patency, till last follow up. The following details were noted: 1) patient characteristics – age, gender, primary renal diagnosis, indication for dialysis, 2) catheter details – catheter size, laterality, catheter type, 3) incidence of catheter-related complications including infection, thrombus, and mechanical issues, and 4) survival of catheter until removal and infection free survival of the catheters. Patients were categorized into two groups. The first group (A) underwent “premature catheter removal” due to the various catheter-related complications and the second group (B) consisting of those who were without premature catheter removal, that is, catheters were removed when it was no longer needed or remained functional till the last follow up. The study was approved by the institutional ethics committee of the hospital.

Results

Forty-five TCCs inserted were studied for 12,590 catheter days. Of the 48 TCCs inserted during the study period, three continued at a different dialysis center within the first 3 months and were excluded from the study [Figure 1]. Apart from these patients, around 18 patients with ESRD were initiated on CAPD but none received a preemptive fistula formation, during the same time frame. Within our cohort, AVF were successfully created in seven patients after an average duration 407 days on a tunneled catheter. Group A included 16 catheters, which were studied for 4978 days and removed prematurely due to catheter failure. Group B included 29 catheters, studied for 7612 days and were either removed electively or were still functioning at the end of the study. Duration of follow up ranged from 8 to 774 days with a median of 306 ± 28 days. There were no missing data as all the relevant catheter details are routinely entered prospectively into predesigned vascular access forms and stored in the medical records. Three patients were lost to follow up after 172, 456, and 488 days, respectively. Catheters in these three were classified into group A or B according to the catheter status observed until the last follow up.

Risk factors for CRBSI

No specific patient characteristic could be identified as a risk factor for CRBSI. Among the catheter characteristics, the insertion site, catheter size, and type had no significant association with CRBSI. Binary logistic regression analysis showed that the presence of thrombus and duration of catheterization were significant predictors of infection. The presence of a thrombus had an OR of 29.51 (95% CI 3.5, 248), P = 0.009 and longer duration of catheterization had an OR of 1.009 per day (95% CI 1.002, 1.016), P = 0.002. [Table 3].

Table 3 Catheter-related infections and their risk factors

	Catheters with infection	Catheters without infection	Relative risk (95% C.I.)	P
Number of catheters	15	30
Age-Mean±SD (yrs)	10.46±2.69	10.01±2.33		0.35
Distribution
<5 yrs, n (%)	1 (6.6)	1 (3.3)	1.5 (0.3,3.6)	0.76
6-10 yrs, n (%)	8 (53.3)	14 (46.6)	1.1 (0.5,2.7)
>11 yrs, n (%)	6 (40)	15 (50)	0.86 (0.35,2)
Gender
Boys, n (%)	11 (73.3)	27 (90)	0.5 (0.24,1.3)	0.15
Girls, n (%)	4 (26.6)	3 (10)
Underlying disease
CAKUTa	10 (66.6)	21 (70)	0.9 (0.4,2.2)	0.82
Non-CAKUT	5 (33.3)	9 (30)
Size of catheter
<12.5 Fr	5 (33.3)	16 (53.3)	0.57 (0.22,1.34)	0.2
≥12.5 Fr	10 (66.6)	14 (46.6)
Site of catheter
R-IJVb, n (%)	12 (80)	24 (80)	1 (0.42,3.02)	1
L-IJVc, n (%)	3 (20)	6 (20)
Type of catheter
Silicone, n (%)	14 (93.3)	22 (73.3)	3.5 (0.8,20.47)	0.23
Polyurethane, n (%)	1 (6.6)	8 (26.7)
Prior hemodialysis catheter inserted at same site, n (%)	4 (26.6)	10 (33.3)	0.81 (0.29,1.9)	0.19
Presence of thrombosis, n (%)	9 (69.2)	4 (13.3)	29.5 (3.5,248.5)**	0.002
Duration of catheterization (median days, IQR)	362 (316,450.5)	187.5 (81,339.3)	1.009 (1.002,1.009)**	0.009
Catheter failure, n (%)	12 (80)	4 (10)	8 (2.9,23.9)	<0.001

^aCAKUT, Congenital Anomalies of Kidney and Urinary tract; ^bR-IJV, Right Internal jugular vein; ^cL-IJV, Left internal jugular vein, **Odds ratio (95% C.I.) derived from the binary regression

The construction of the ROC curve showed an area under the curve of 0.808 for duration of catheterization as a predictor for risk of CRBSI and identified 267 days as the cut-off point with a sensitivity of 93% and a specificity of 66.7% [Figure 2]. Infection free catheter survival for the group was a mean of 449 ± 42 days with 65% infection free survival at 360 days. The infection free survival at 360 days was 50% for group A vs 84.2% for group B (P = 0.03) [Figure 3].

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Figure 2

ROC curve predicting a cut-off value of catheter duration for infection. area under the curve = 0.808 (P = 0.001), determined a cutoff for the duration of catheterization to predict infection to be 267 days. (Sensitivity = 93%, Specificity = 66.7%)

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Figure 3

Kaplan– Meir charts comparing infection-free survival in catheter failure (group A), elective removal (group B), and cumulative group. KM curves showing cumulative survival of the total group (green) showing mean survival of 449 ± 42 days with survival 95%@90 and 180 days, 91.5%@ 270 days, and 65.5% @ 360 days; KM curves showing infection free survival of group A (blue) with mean survival of 388 ± 38 days with 100% survival at 90 and 180 days, 91.7% @270 days, and 50% @360 days and group B (red) with mean survival of 593 ± 43 days with 92.6% @ 90,180, and 270 days, 84.2% @360 days. (P = 0.03)

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Discussion

Median catheter survival in our cohort was 306 ± 28 days. Catheter failure, defined as unplanned premature removal due to catheter-associated complications, occurred in one-third of all catheters and CRBSI being responsible for three-fourths of catheter failures. The predominant organisms isolated in our patients were gram-negative bacteria accounting for 80% of all organisms, half of which were due to pseudomonas. Staphylococci accounted for only two cases in our study. Thrombus within the catheter was seen in more than two-thirds of the catheters with CRBSI and had a high predictive value for the presence of CRBSI. The overall mortality in the cohort was 25% with 19% attributed to sepsis related to CRBSI. Infection free catheter survival was greater than 90% during the first 270 days but dropped to 65% by 360 days. The duration of catheterization of 267 days was identified as a significant cut-off for the risk of CRBSI.

The CRBSI rate in our study was 1.19 per 1000 catheter days, which was comparable to those reported in many other studies [Table 4].[21314] In the study by Goldstein et al.,[24] the CRBSI rate was 0.71 per patient year and was the cause for catheter failure in 36% of cases with no related mortality. The low prevalence had been attributed to strict adherence to aseptic protocols. Mortality secondary to CRBSI was higher (1.6%) than reported in other studies,[25] probably due to nature of causative organism. Similar gram-negative predominance has been shown only in one of the adult studies from South Asia with 40% resistant strains.[26] On the contrary, most pediatric studies have reported staphylococci to be the most frequent bacterial isolate.[112728]

No patient characteristic or catheter characteristic could be identified as a risk factor for CRBSI. Though young age has been reported as risk factor in most studies, the Italian registry along with few others showed a lower prevalence of CRBSI in children less than 2 years of age.[12293031] Our study had only two children aged less than 5 years, making this finding difficult to assess. Hypoalbuminemia and immunosuppression have been identified as risk factors for CRBSI in some studies.[303233] Although we did not specifically address these issues, the incidence of CRBSI was similar in those with CAKUT and non-CAKUT as the underlying primary renal disease. Catheter-related risk factors included the site of catheter insertion, with femoral vein and left IJV being more susceptible.[34] Other factors incriminated were duration of catheterization and past catheter-related bacteraemia.[323536] Eighty percent of our patients had a right IJV insertion, and none with femoral access; hence, we could not assess relevance of site of insertion. No significant difference was found in incidence of CRBSI based on the type of catheter used, but only one-ninth Bard catheters developed CRBSI and none of them failed. This catheter was available only in larger size (14.5 Fr) and hence used only in older children. However, the numbers are too few to assess its significance.

A positive correlation between mural thrombi and infection had also been noted by Raad et al.[37] However, the temporal relationship between the thrombus and CRBSI could not be ascertained due to the retrospective nature of the study. We did not come across a fibrin sheath leading to obstruction.

The safe duration of catheterization has not been addressed in many studies, but similar critical cut off of 9 months was shown by Goldstein et al.[24] Hence, in lieu to the cut off in our study of 267 days, early AVF formation can prevent the infectious complications. Mechanical complications accounted for one-fourth of all catheter failure in our patients, though have been significantly higher accounting for 23–81% of the catheter failures.[10121331]

Indian children with ESRD who do not have an eligible kidney donor in the family have a long dialysis vintage, as the waiting period for cadaveric donation can be longer than 5 years. The survival to transplantation is dependent not only on patient characteristics and access to good nephrology care but also on the survival of the tunneled catheter. Mortality is known to be significantly higher in children on dialysis than in those with transplantation.[438] In developed countries that have had maintenance HD for several decades, a reduction in mortality has been seen after each successive 5-year period with many countries having a mortality rate less than 5% for children on maintenance dialysis.[39404142] In contrast, high mortality rates greater than 20% has been reported from many resource limited nations including India.[1543] Constraints in India include the lack of trained nurses and technicians for pediatric dialysis, late diagnosis, poor nutritional state of the patients, and the need to self-pay for dialysis care at many centers.

There are several limitations of our study. It is a single center study with a small sample size, which limits the generalizability of results. The study is retrospective in nature with its inherent bias and inability to establish a temporal relationship of risk factors. Other long-term complications of tunneled catheters such as fibrin sheath formation, central vein stenosis, access recirculation, and flow limitations that may adversely impact the quality of dialysis were not addressed in our study. Our study could not identify significant patient or catheter-related risk factors for catheter failure, probably because of the small sample size and retrospective nature of the study. Prospective large studies may help to identify other risk factors for CRBSI (like age, thrombosis, site) and define the role of different catheter types in the prevention of infection.

In conclusion, despite the significant risk of adverse events, tunneled catheters remain a viable option for maintenance HD in children, even in resource limited settings, as 75% of children survived at the end of 6 years with successful transplantation in one-fourth of the children. CRBSI is the main reason of catheter failure. Early creation of A-V fistula must be a reasonable necessity aiming at preventing infectious complications.