A protocol of urokinase infusion and warfarin for the management of the thrombosed haemodialysis catheter

Alan Webb, Mubarak Abdalla and Gavin I. Russell

Renal Unit, North Staffordshire Royal Infirmary, Princes Road, Hartshill, Stoke-on-Trent, UK

Abstract

Background. Catheter dysfunction remains a significant cause of catheter loss and interrupted haemodialysis sessions. A number of regimens utilizing urokinase have been used but the optimum management of this common problem remains undetermined.

Methods. The study took place over 2 years and evaluated a protocol of urokinase infusion (25 000 U in 48 ml saline run at 4 ml/h via each limb of the catheter) followed by warfarin for restoration of catheter patency.

Results. Forty-eight urokinase infusions were used for 41 episodes of catheter dysfunction. Catheter patency was restored in 95% and only one catheter was lost. Recurrent thrombosis occurred in eight of 10 catheters not anticoagulated. Once anticoagulated, catheters worked well. Further episodes of non-function were related to a sub-therapeutic INR.

Conclusions. Our results show a high success rate for our protocol. We suggest an aggressive approach to the management of catheter thrombosis with urokinase used by infusion and carefully controlled anticoagulation to maintain the INR in the range 2–2.5.

Keywords: anticoagulation; catheter dysfunction; tunnelled lines; urokinase; warfarin

Introduction

Increasingly, tunnelled cuffed catheters are used to provide haemodialysis access. This is likely to continue as older and more diabetic patients are taken onto dialysis. Various types of tunnelled line can be used, such as the Permcath [1] or Tesio system [2]. If these catheters are to provide long-term access they need to provide reliable blood flows and have low complication rates.

Catheter dysfunction is defined as the failure to attain and maintain an extracorporeal blood flow, which allows for adequate dialysis. This is a frequent problem resulting in the loss of up to 33% of catheters [3,4]. Whilst initial malfunction is usually related to mechanical problems, later dysfunction is usually the result of thombosis, which maybe intra-luminal or around the catheter [5], the latter often being referred to as a fibrin sheath [6]. A number of studies using thrombolytic agents for the management of catheter dysfunction have been reported. These vary from simple locking of the catheter [7] to high dose infusions between treatments or during the dialysis period [8,9]. Variable success rates are reported for these regimens. The use of subsequent anticoagulation is also debated.

Because of increasing use of tunnelled catheters in our unit, we adopted a protocol of urokinase infusion followed by anticoagulation for the management of catheter dysfunction. This study reports our results.

Subjects and methods

During the period February 1998 to February 2000 all episodes of catheter dysfunction were studied (blood flow inadequate to support haemodialysis). Only dysfunction of tunnelled lines (Permcaths and Tesio lines), were included in the study.

All catheters were routinely locked with heparin (5000 U/ml) between dialysis sessions. For each episode of catheter dysfunction the catheter was locked with urokinase (5000 U each limb) to the total volume of the catheter and left for a period of 4 h. The catheter was then retried. Failure to unblock the catheter was followed by admission to hospital and an infusion of urokinase (25 000 U in 48 ml of saline run at 4 ml/h via each limb of the catheter, i.e. a 12 h infusion to each limb of the catheter). This was repeated up to a maximum of three times (Figure 1Go). Successful restoration of catheter patency was followed by anticoagulation with warfarin to maintain an INR between 2 and 2.5.



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Fig. 1. Protocol for the management of the non-functioning Permacath or Tesio line.

 

Results

A total of 48 urokinase infusions were used for 41 episodes of catheter dysfunction. All patients had failed to respond to simple locking of the catheter. These 48 infusions were used in 23 catheters (eight Permcaths and 15 Tesio lines), in 21 patients.

Thirty-seven episodes responded to a single infusion of urokinase. Two episodes to two infusions and two catheters required three consecutive infusions. Flow from one catheter was still not satisfactory at the end of the infusions and subsequently underwent fibrin stripping with good result. One catheter failed to respond to a single urokinase infusion and was lost. Therefore, the protocol was successful in 95% of episodes. Only one catheter was lost (4%).

The mean time from catheter insertion to non-function was 110 days (range 3–425). Twenty-eight episodes (68%) occurred while the catheter had been in situ for less than 2 months. Twenty episodes occurred prior to anticoagulation. Unfortunately 10 of these episodes were not followed by anticoagulation, resulting in repeat dysfunction in eight. Thirteen episodes occurred while the patient was receiving anticoagulation. In 11 of these the INR had become sub-therapeutic, with a mean INR of 1.46.

Overall, therefore, this protocol of urokinase infusion restored catheter patency in 39 (95%); with the result that only one catheter was lost (2%), and one required fibrin sheath stripping. The protocol was well tolerated with no bleeding complications related to either urokinase infusion or the use of anticoagulation. No increase in the use of erythropoietin or i.v. iron was observed in anticoagulated patients.

Discussion

This study describes our experience with a protocol of urokinase infusion administered over 12 h, followed by anticoagulation for the management of the thrombosed catheter. It demonstrates good patency rates and thus catheter salvage, the majority of catheters requiring only a single infusion. We found locking of the catheter to be unsuccessful in restoring catheter patency, similar to Twardowski [9]. Given that intra-luminal clot is not the primary reason for catheter blockage [10], and that thrombosis occurs primarily around the catheter, this provides the rationale for the use of an infusion method. A urokinase lock may exhibit a temporary effect by partially dissolving the thrombus but this then effectively ‘regrows’ around the catheter, requiring further urokinase. The dose of urokinase used for this protocol was relatively low (50 000 U in total), others series employing much higher doses, e.g. 250 000 U [9]. Our success may relate to the slow rate of infusion via the catheter, although this has the disadvantage of requiring hospital admission and delayed dialysis. Intra-dialytic urokinase was not used, as catheter flows could not support dialysis.

The majority of episodes of catheter dysfunction (68%) occurred within the first 2 months of catheter placement. In another series, mean duration of catheter usage before blockage was 39 days [11]. This suggests that thrombus formation occurs early after catheter placement. As an observation we have found that catheter flows in the first 2–3 dialysis sessions are often sub-optimal, followed by spontaneous improvement. A study of 60 Tesio catheters reported initial poor flows in 43%, followed by improvement, although 13% of catheters required intervention in the first 2 weeks [12].

In this study we utilized warfarin following an episode of catheter thrombosis. Of those catheters, which were successfully unblocked, but not anticoagulated, 80% developed recurrent dysfunction, suggesting that without formal anticoagulation the thrombus will redevelop. A similar problem has been described after successful fibrin stripping when warfarin was not prescribed despite initial success of the procedure [13]. It has been suggested that low-dose warfarin could maintain catheter patency [14]. This is not our experience. We suggest an INR maintained in the range 2–2.5. If the INR becomes sub-therapeutic there is a significant risk of catheter dysfunction. In our series this was mainly related to temporary discontinuation of warfarin for surgical procedures such as access surgery. During these periods the catheter could be locked with a thrombolytic agent between dialysis sessions. Recombinant tissue plasminogen activator has been shown to be superior to heparin for catheter locking [15] and could be used in this situation whilst awaiting re-anticoagulation.

In summary we describe a protocol of urokinase infusion followed by warfarin for the management of the blocked haemodialysis catheter, which was successful in virtually all catheters. This has major benefits in terms of catheter survival and preservation of access sites, which offsets the cost of admission and delayed dialysis. It is well tolerated without the need for more invasive procedures such as fibrin stripping. We found the locking method to be unsuccessful and would suggest abandoning it in favour of an infusion regimen, although the optimal dose remains undetermined. Given that the majority of catheters will re-block, follow up treatment with warfarin is mandatory and should be continued for the life of the catheter. Indeed the success of the protocol is largely determined by maintaining the INR within a therapeutic range and we would suggest 2–2.5.

Notes

Correspondence and offprint requests to: Dr A. T. Webb, Consultant Nephrologist, St Lukes Hospital, Little Horton Lane, Bradford BD5 0NA, UK. Email: alan.webb{at}bradfordhospitals.nhs.uk Back

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Received for publication: 13.11.00
Revision received 1. 6.01.



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