Abstract: 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. 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.

Plain-language summary: 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.