Risk factors associated with hemodialysis central venous catheter malfunction; a retrospective analysis of a randomized controlled trial

Central venous catheters (CVC) are commonly used to establish access in adult North American hemodialysis patients. CVC malfunction is a common clinically encountered complication of the use of tunnelled CVC. Previous authors have identified patient and CVC characteristics associated with malfunction.

In this pre-specified, post-hoc analysis of data from a randomized controlled study we found that patient characteristics were not associated with risk of CVC malfunction after adjusting for hemodialysis session characteristics. Further research is required to predict CVC malfunction and strategies for prevention.

Current guidelines recommend hemodialysis (HD) vascular access via an arterio-venous fistula. However, central venous catheters (CVC) are used by approximately 70% of incident HD patients in North America [1–5]. Complications associated with CVC use include thrombosis and decreased dialysis adequacy due to catheter malfunction [6–8]. These complications are associated with increased healthcare resource utilization; up to 50% of all tunnelled CVC’s fail within one year [9–12].

CVC locking solutions are used in the interdialytic period to decrease the risk of complications; the optimal strategy to minimize CVC complications remains to be determined [13–16]. We previously reported that using once-weekly rt-PA as a locking solution leads to a two-fold reduction in CVC malfunction, compared with thrice-weekly heparin [17]. However, given the potential costs associated with this strategy, its use and uptake may be limited. Identifying patients at greatest risk of CVC malfunction would permit targeted use of this strategy. Using data from the prior randomized trial [17] we sought to determine the association between patient characteristics and CVC-related variables during a dialysis session and the outcome of CVC malfunction.

The subjects and design of the original trial have been described previously [18]. In summary, adult HD patients with newly inserted tunnelled, upper venous system HD catheters were eligible. Subjects were excluded if they were on systemic anticoagulation, undergoing current antibiotic use for catheter related bacteremia, the CVC was inserted via guidewire exchange, or they had risk factors for increased bleeding. If patients with catheter-related bacteremia completed antibiotic treatment, and remained bacteremia free for three hemodialysis sessions, they were eligible. CVC reversal was permitted for up to three consecutive hemodialysis sessions after which the study protocol mandated the CVC run in the non-reversed orientation and the patient was then eligible for the primary outcome.

The study was conducted in adherence with the Declaration of Helsinky, approved by the research ethics board of each institution, and patients provided written, informed consent. Patients were randomized to either thrice-weekly catheter locking solution with heparin (5000 u/mL, full luminal volume), or substitution of the mid-week heparin with recombinant tissue plasminogen activator (rt-PA) (1 mg in 1 mL with saline to full luminal volume) and standard heparin catheter locking solution following the other dialysis sessions. All other HD care was per site-specific protocols.

CVC malfunction (the primary outcome) was defined as: peak blood flow less than 200 mL/min for thirty minutes during a HD session; mean blood flow less than 250 mL/min for two consecutive HD sessions; inability to initiate HD [19]. Each patient was followed-up for six months. Patients were censored at the first of: study end, removal of the CVC, initiation of alternative renal replacement therapy, or transfer to a centre not involved in the trial.

In this pre-specified post-hoc analysis of data from a randomized controlled study we quantified the risk for CVC malfunction conferred by routinely observed and monitored patient and HD session characteristics. We found a significant increased risk when a reduction in litres of blood processed and mean blood flow over a two-week period occurred, however there was no association between baseline patient characteristics and risk of CVC malfunction.

CVC malfunction is the most common cause for CVC removal [20–22]. However, few studies have identified and quantified risk factors or predictors of CVC malfunction. Previous studies of patients with tunnelled CVCs reported that diabetic status and prior CVC exposure were associated with malfunction [12, 23]. However, data lacking on malfunction definition, locking solution, and the inclusion of infections and non-infectious criteria for CVC removal make extrapolation of these results difficult. While CVC location has been identified as a risk factor for malfunction, this study examined non-tunnelled catheters only [24]. An observational cohort study of 3,364 incident and prevalent HD patients with a CVC in the United States reported the risk of CVC malfunction (blood flow <300 mL/min) was lower for males and black race (compared with white) and higher if CVC was not the first access modality [25]. Male patients in our study were also at decreased risk but, possibly due to small numbers, we saw no significant effect of first CVC ever or ethnicity.

We analysed six sessions (a two week period) as we felt it would encompass a reasonable timeframe for clinicians to review dialysis characteristics in real-world practice; potentially guiding decision-making to pre-empt malfunction. In univariate analysis we found the strongest risk factor for CVC malfunction was CVC reversal in the prior HD session, or any of the six sessions prior to malfunction. However, our study protocol limited the number of consecutive sessions that could be performed in the reversed position to three, therefore this variable was included as a potential confounder in the adjusted analysis rather than an independent predictor given its potential relationship with the outcome. KDIGO Guidelines [19] suggest that CVC reversal be a temporary solution to managing malfunction, and authors have found that one third of patients may routinely undergo dialysis with their catheters in the reversed position [26]. This prevalence may be influenced by studies questioning the impact of CVC line reversal or blood flow on dialysis adequacy. Carson et al. noted CVC reversal improved clearance, despite increased recirculation, if the blood flow through the CVC concurrently increased to an average 315 mL/min [27] and Moist et al. reported decreased blood flow through reversed CVCs did not significantly affect online urea clearance if blood flow was greater than 250 mL/min [28]. Our results corroborate these findings as adjusted subgroup analysis by blood flow or blood processed quartile found a statistically significant increased risk when blood flows were less than 325 mL/min or total blood processed was less than 65 L per session in the preceding six sessions to a malfunction event.

We sought to pragmatically identify HD session characteristics that may signal an increased risk of CVC malfunction, and warrant consideration for early intervention. Decreased blood flow below 325 mL/min or total blood processed less than 65 L per session averaged over six sessions may therefore signal early or mild CVC malfunction. Mechanistically, it is plausible that a developing CVC thrombus or fibrin sheath, partially obstructing the CVC, and will decrease the average blood flow and blood processed. Interventions such as thrombolytics, catheter stripping, or catheter exchange may be required to improve CVC function, although these interventions are associated with costs, and long term catheter patency rates are suboptimal irrespective of intervention chosen [29, 30]. CVC reversal, decreased blood flow, or decreased blood processed may herald the future onset of severe malfunction (as defined by blood flow criteria), although whether interventions to identify and treat these patients is feasible, improves outcomes, or is cost effective requires further investigation.

Our study has limitations. First, this is a post-hoc analysis, and the definition of CVC malfunction included blood flow as a criteria (a significant predictor of the malfunction outcome), which may lead to an overestimate of the true effect of blood flow as a predictor. Secondly, our protocol limited the number of sessions that could be performed with a CVC in the reversed position. At the time of our study, CVC reversal was believed to result in a reduction in dialysis adequacy. CVC reversal was the strongest risk factor in our univariate analysis, therefore future studies could prospectively evaluate this association over longer time periods. Finally, the generalizability of these results to other units where trisodium citrate is used as a locking solution may be limited.

In conclusion, we found that HD session characteristics related to blood flow and blood processed were associated with an increased risk of CVC malfunction, while patient characteristics were not. Further study is needed to determine if the routine use of rt-PA as a locking solution in patients at increased risk of CVC malfunction will result in clinical and economic benefit.