What is the issue?
Patients who rely on haemodialysis due to kidney failure require vascular access and although not optimal, a tunnelled haemodialysis catheter is frequently used. Unfortunately, along with infection issues these lines are prone to dysfunction due to clotting and fibrin sheath formation. Medications such as alteplase have a recognised role in preventing line dysfunction but the best approach to treating established line dysfunction has not been found.
What did we do?
We searched Cochrane Kidney and Transplant's Specialised Register up to 17 August 2017 and performed a systematic review of studies performed in patients with dysfunctional haemodialysis catheters and compared the success of thrombolytic agents, fibrin sheath stripping and line replacement.
What did we find?
We found eight studies involving 580 participants that tested the three different treatments. Studies also compared drug dosages and methods of administration. The quality of evidence is limited by small study size and high risk of bias. Thrombolytic therapy was probably better than placebo at restoring catheter function but there was no optimal dose or administration method. Physical disruption of a fibrin sheath may be equally effective as pharmaceutical thrombolytic agent for immediate management of catheter dysfunction. Catheter patency at two weeks is probably better following fibrin sheath stripping or catheter exchange compared to thrombolytic agent. Catheter exchange may be better than sheath disruption for long-term catheter survival and the use of both techniques together is probably best. There is currently insufficient evidence favouring any technique in terms of either dialysis adequacy or reduced risk of adverse events.
Further research is required to adequately address the question of the most effective technique for haemodialysis catheter dysfunction.
Thrombolysis, fibrin sheath disruption and over-the-wire catheter exchange are effective and appropriate therapies for immediately restoring catheter patency in dysfunctional cuffed and tunnelled HD catheters. On current data there is no evidence to support physical intervention over the use of pharmaceutical agents in the acute setting. Pharmacological interventions appear to have a bridging role and long-term catheter survival may be improved by fibrin sheath disruption and is probably superior following catheter exchange. There is no evidence favouring any of these approaches with respect to dialysis adequacy or risk of adverse events.
The current review is limited by the small number of available studies with limited numbers of patients enrolled. Most of the studies included in this review were judged to have a high risk of bias and were potentially influenced by pharmaceutical industry involvement.
Further research is required to adequately address the question of the most efficacious and clinically appropriate technique for HD catheter dysfunction.
Adequate haemodialysis (HD) in people with end-stage kidney disease (ESKD) is reliant upon establishment of vascular access, which may consist of arteriovenous fistula, arteriovenous graft, or central venous catheters (CVC). Although discouraged due to high rates of infectious and thrombotic complications as well as technical issues that limit their life span, CVC have the significant advantage of being immediately usable and are the only means of vascular access in a significant number of patients. Previous studies have established the role of thrombolytic agents (TLA) in the prevention of catheter malfunction. Systematic review of different thrombolytic agents has also identified their utility in restoration of catheter patency following catheter malfunction. To date the use and efficacy of fibrin sheath stripping and catheter exchange have not been evaluated against thrombolytic agents.
This review aimed to evaluate the benefits and harms of TLA, preparations, doses and administration as well as fibrin-sheath stripping, over-the-wire catheter exchange or any other intervention proposed for management of tunnelled CVC malfunction in patients with ESKD on HD.
We searched the Cochrane Kidney and Transplant Specialised Register up to 17 August 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov.
We included all studies conducted in people with ESKD who rely on tunnelled CVC for either initiation or maintenance of HD access and who require restoration of catheter patency following late-onset catheter malfunction and evaluated the role of TLA, fibrin sheath stripping or over-the-wire catheter exchange to restore catheter function. The primary outcome was be restoration of line patency defined as ≥ 300 mL/min or adequate to complete a HD session or as defined by the study authors. Secondary outcomes included dialysis adequacy and adverse outcomes.
Two authors independently assessed retrieved studies to determine which studies satisfy the inclusion criteria and carried out data extraction. Included studies were assessed for risk of bias. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using GRADE.
Our search strategy identified 8 studies (580 participants) as eligible for inclusion in this review. Interventions included: thrombolytic therapy versus placebo (1 study); low versus high dose thrombolytic therapy (1); alteplase versus urokinase (1); short versus long thrombolytic dwell (1); thrombolytic therapy versus percutaneous fibrin sheath stripping (1); fibrin sheath stripping versus over-the-wire catheter exchange (1); and over-the-wire catheter exchange versus exchange with and without angioplasty sheath disruption (1). No two studies compared the same interventions. Most studies had a high risk of bias due to poor study design, broad inclusion criteria, low patient numbers and industry involvement.
Based on low certainty evidence, thrombolytic therapy may restore catheter function when compared to placebo (149 participants: RR 4.05, 95% CI 1.42 to 11.56) but there is no data available to suggest an optimal dose or administration method. The certainty of this evidence is reduced due to the fact that it is based on only a single study with wide confidence limits, high risk of bias and imprecision in the estimates of adverse events (149 participants: RR 2.03, 95% CI 0.38 to 10.73).
Based on the available evidence, physical disruption of a fibrin sheath using interventional radiology techniques appears to be equally efficacious as the use of a pharmaceutical thrombolytic agent for the immediate management of dysfunctional catheters (57 participants: RR 0.92, 95% CI 0.80 to 1.07).
Catheter patency is poor following use of thrombolytic agents with studies reporting median catheter survival rates of 14 to 42 days and was reported to improve significantly by fibrin sheath stripping or catheter exchange (37 participants: MD -27.70 days, 95% CI -51.00 to -4.40). Catheter exchange was reported to be superior to sheath disruption with respect to catheter survival (30 participants: MD 213.00 days, 95% CI 205.70 to 220.30).
There is insufficient evidence to suggest any specific intervention is superior in terms of ensuring either dialysis adequacy or reduced risk of adverse events.