In-Depth Reviews

Catheter Management in Hemodialysis Patients:

Delivering Adequate Flow
Anatole Besarab and Rahul Pandey

Summary
Over 330,000 individuals in the United States depend on hemodialysis (HD), the majority as a result of end-
stage renal disease. Sustainable vascular access can be achieved through arteriovenous fistulas, arteriovenous
Division of Nephrology
grafts, or tunneled catheters. Tunneled dialysis catheters (TDCs) often remain in use for months or even and Hypertension,
years, long beyond their initial intended use as a bridging device. Research efforts are focused on identifying Department of
strategies to prevent/minimize the risk of the most common catheter-related complications: thrombotic oc- Medicine, Henry Ford
clusion and infection. Thrombotic occlusion of TDCs prevents adequate dialysis but can be managed success- Hospital, Detroit,
Michigan
fully through thrombolytic agents to restore/improve blood flow in the majority of patients, allowing immedi-
ate HD delivery and prolonging usability of the TDC. Occasionally, catheter exchange with fibrin sheath
Correspondence:
disruption is needed to preserve the site. Surface-treated catheters could improve the morbidity and mortality Dr. Anatole Besarab,
associated with HD delivery via an indwelling catheter, but results from studies have been disappointing to Division of Nephrology
date. We review the etiology of catheter-based access failure and the monitoring and interventional steps that and Hypertension,
should be taken to maintain the patency and safety of catheters for HD. Wherever possible we note the areas Department of Medicine,
Henry Ford Hospital,
in which there is scant data where further randomized clinical trials are needed. 2799 West Grand
Clin J Am Soc Nephrol 6: 227–234, 2011. doi: 10.2215/CJN.04840610 Boulevard, Detroit, MI
48202. Phone: 313-916-
2713; Fax: 313-916-
2554; E-mail: abesara1@
Introduction den (13,14). A retrospective analysis of resource use hfhs.org
Hemodialysis (HD) is a life-saving and life-sustaining among 88 HD patients found that 51% experienced at
procedure. In 2006, approximately 330,000 individu- least one access-related complication during fol-
als in the United States were receiving HD (1). Sus- low-up (mean 487 days) (15). A follow-up of 674
tainable vascular access providing high-volume blood patients from 22 chronic HD units showed a signifi-
flow rates (Qb) ⬎300 ml/min is essential, either cant association between decreased dialysis adequacy
through permanent arteriovenous access or tunneled and increased hospitalization because of complica-
dialysis catheters (TDCs) (2). The majority of patients tions (11%), number of hospital days (12%), and in-
begin HD with a TDC (3). In the United States, 60 to patient expenditure (US$940) (16). Of all accesses,
82% of incident HD patients start with a catheter (4,5). TDCs produce the majority of problems related to
Up to 33% of patients in Canada are dialyzing with a delivering adequate blood flow for dialysis and re-
long-term TDC (6). quire the most interventions (2,5).
TDCs allow immediate vascular access, are initially
almost always functional, require no venipunctures,
Defining Access Dysfunction
rarely produce hemodynamic consequences, and do
The 2006 National Kidney Foundation Kidney Di-
not require surgical placement (7). Despite efforts to
alysis Outcomes Quality Initiative (KDOQI) guide-
limit their use, TDCs often remain in use for months
lines define access dysfunction as the inability to
or even years (8). Studies have shown that approxi-
achieve Qb of ⱖ300 ml/min (2) during the first 60
mately 40% of patients had TDCs 90 days after com-
minutes of HD despite at least one attempt to improve
mencing HD (5,9,10).
flow. Since then, larger bore catheter design allows
Proper catheter management to preserve patency
much higher Qb (⬎400 ml/min) to be achieved at the
and to prevent/minimize the risk of infection is vital
same prepump pressure. Waiting until Qb declines to
in improving patient outcomes (11). This article fo-
300 ml/min in these catheters may be inappropriate,
cuses on the first of these, reviewing the etiology of
missing the opportunity to detect catheter dysfunc-
inadequate blood flow delivery and discussing the
tion earlier. However, studies to support this hypoth-
monitoring and interventional steps needed to main-
esis are needed.
tain the patency and usability of HD catheters.

Causes of Occlusive Access Dysfunction

Access Dysfunction
The consequences of blood flow access dysfunction
in HD can vary from inadequate dialysis dose deliv-
ery to increased mortality (1,12). Access dysfunction
increases resource utilization and healthcare-cost bur-
www.cjasn.org Vol 6 January, 2011
Early identification of catheter dysfunction enables
prompt intervention and salvage. Catheter occlusion,
a main cause of poor Qb, may be caused by kinking or
malpositioning (17). In these cases, catheter dysfunc-
tion generally emerges during the first HD session
Copyright © 2011 by the American Society of Nephrology 227
228 Clinical Journal of the American Society of Nephrology

and can be resolved by repositioning or, occasionally,
replacing the catheter. In a previously well function-
ing long-term catheter, inadequate flow may result
from a change in position of the catheter tip during
that session and respond to simply placing the patient
in a recumbent position or adjusting the patient’s
neck position.
However, thrombotic occlusions, of which there are
four major types (Table 1) are a more serious cause of
access dysfunction. They occur in 30 to 40% of pa-
tients, can occur within 24 hours after insertion or
after prolonged continuous successful usage (18), and
can provide a substrate for bacterial growth (19). A
study of 721 HD patients revealed that clot formation
was one of four parameters, significantly (P ⬍ 0.001)
and independently related to inadequate dialysis
dose delivery (20).
Pathophysiology of Catheter Dysfunction
Injury to the vessel endothelium begins with inser-
tion of the catheter and is augmented by turbulent
flow around the catheter. “Line” reversal or catheter
”manipulation” as attempts to improve blood flow
promote even more disruption in the fibrinolytic sys-
tem, initiating the coagulation and inflammatory cas-
cade (21). Minute irregularities on the catheter poly-
mer surface permit platelet adhesion and activation of
the intrinsic coagulation pathway (17). Silicone may
have less throbogenic potential than other materials (22).
It is the development of a fibrin sheath that deter-
mines the long term patency of a catheter. This sheath,
initially composed of fibrinogen, albumin, lipopro-
teins, and coagulation factors, begins to form within
24 hours of insertion (23). The fibrin sheath attracts
platelets and coagulation factors and promotes leuko-
cyte adherence (21). Over weeks and months, collagen
is deposited as smooth muscle cells from the venous
vessel wall migrate toward the tip. The rate of these
processes varies among patients because of inherited
or acquired characteristics. Ultimately, if clotting in
excess of the endogenous fibrinolytic system’s capac-
ity develops, catheter thrombosis occurs.
Monitoring for Access Dysfunction
Prompt identification of access dysfunction, a key
goal of the KDOQI guidelines (24), enables appropri-
ate intervention (pharmacologic or mechanical) be-
fore the emergence of access- and life-threatening
complications. Prospective monitoring for catheter
Qb dysfunction should be a routine part of the med-
ical management of patients undergoing HD. Poten-
tially dysfunctional catheters and reduction of Qb to
“critical” levels can be detected before “emergency”
problems arise through systematic monitoring of Qb
and prepump negative arterial pressure (Pa) during
HD. The catheter channel is a long tube whose diam-
eter and length determine resistance to flow (25).
There is a curvilinear relationship between pressure
and flow; the prepump pressure is virtually a nega-
tive mirror of the venous pressure at Qb from 50 to
500 ml/min (Figure 1a). Most large-gauge catheters
have a conductance (Qb/Pa) of 2 ml/min/mmHg.
When examined serially over time at a prescribed Qb
(e.g. 350 to 450 ml/min), increasing negative prepump
pressure to achieve the prescribed flow reflects alter-
ations in inlet orifice TDC function.
We recommend the measurement of Qb at a preset
prepump pressure (e.g. ⫺250 ⫾ 10 mmHg at each HD
session 5 minutes after the start of each HD session
with trending over time. A Qb decline of ⬍10% at the
same negative prepump pressure may result from
many factors, but a change ⬎10%, particularly if pro-
gressive, i.e. lower conductance, suggests impending
access dysfunction, which may warrant intervention
(Figure 1b).
Qb decline to ⬍300 ml/min during the first and/or
last 30 minutes of an HD session, delivered Kt/V of
⬍1.2, Pa more negative than 250 mmHg, and venous
pressure of ⬎250 mmHg are other signs of dysfunc-
tion. Routine monitoring of these parameters with

Table 1. Types of thrombotic occlusions

Type Features Symptoms

Fibrin tail or flap Fibrin extends from the end of the
catheter causing partial occlusion
(fibrin tail acts as one-way valve)
Fibrin sheath Fibrin adheres to the external surface
encasing the catheter, possibly
extending the length of the catheter;
thrombi trapped between sheath
and catheter tip
Mural thrombus Fibrin from vessel wall injury binds to
fibrin-covered catheter; increased
risk of venous thrombosis
Intraluminal Fibrin forms inside catheter lumen
thrombus causing partial or complete
occlusion
Ability to infuse but not
withdraw blood
Inability to infuse and/or
withdraw blood
Leakage of infusate from the
insertion site, swelling,
pain, tenderness, engorged
vessels
Inability to infuse and/or
withdraw blood
Clin J Am Soc Nephrol 6: 227–234, January, 2011
a)
250
200
150
Pv
Pressure (mmHg)
100
50


(1000 versus 10,000 U/ml) heparin lock was associated
0


 with a higher use of tissue plasminogen activator
-50
-100
Pa
-150
-200
-250
0 50 100 150
b) 2
1.5
Qb/Pa 1 thrombolytic therapy, or safety (38). A subsequent
0.5
0 solution (39).
0 1
Figure 1. | (a) Relationship of prepump pressure (Pa) and ve-
nous return pressure (Pv) to blood pump flow. Note that the
two curves are nearly mirror images of each other, although
the negative Pa pressure has an absolute value slightly higher
than Pv. The dashed lines shows the effect of orifice obstruc-
tion at either the inflow or outflow ports. The circles indicate
the effect of “deliberate” clamping of the tubing to the arterial
transducer to obviate machine alerts. Prepump pressure be-
comes independent of flow. (b) Sequential measurements of
pump flow (Qb) at the same prepump pressure early into
dialysis.
immediate alerts to physicians should be encouraged
for all HD patients with a TDC.
Maintaining Patency with Catheter Locking Solutions
between Dialysis Sessions
The standard procedure for maintaining patency
between dialysis treatments has been heparin instil-
lation (1000 to 10,000 U/ml) into the lumens in a
volume sufficient to fill to the lumen tip (the lock).
The heparin concentration used for locking has been
reduced because catheter lumens have increased in
volume so as to reduce the possibility of unintentional
systemic anticoagulation of patients (26 –29). Locking
with lower heparin concentrations (2500 or 1000
U/ml) prevents catheter thrombosis as efficiently as
5000 U/ml (30,31). Heparin loss (“leak phenomenon”)
through diffusion from the lumen within the first
hour or after injecting the locking solution (slow ver-
sus fast) may accidentally administer up to half the
anticoagulant systemically (27) and may explain re-
ports of bleeding episodes after heparin lock (32,33).
No catheter seems to be free of this problem. An in
vitro study of five different double lumen catheters
showed that systemic leakage was greatest with 20%
overfill (34).
The degree of systemic anticoagulation appears to
be proportional to the dose of heparin instilled. In a
small study in patients undergoing heparin-free dial-
ysis, all patients with catheters and heparin locks at
Hemodialysis Catheter Flow, Besarab and Rahul 229
the end of dialysis had deranged clotting 1 hour after
completion of dialysis. Heparinized saline, using a


lower total dose of heparin per catheter lumen, sig-

nificantly reduced this rate. A lower-concentration






 (tPA) (35). Citrate locks do not produce this apparent




systemic effect (27,29,36).




Currently there is great interest in trisodium citrate
(TSC), given its antithrombotic and potential antibac-
200 250 300 350 400 450 500
Qb (mL/min) terial properties (37). A study in 19 patients (1370
sessions) showed that a low-concentration 4% citrate
lock was associated with a higher rate of catheter
thrombosis than standard heparin but had no effect
on dialysis efficiency, effective blood flow, the use of
double-blind, crossover study in 28 patients showed
that a 5% citrate lock was just as efficacious as a 10%
2 3 4
Months
Two prospective observational studies conducted
in Canada (40,41) showed either equivalence or a
lower rate of TDC exchange and tPA use without a
change in hospitalization for TSC 4% versus heparin.
The largest experience reported is that from Grudz-
inski et al. (42) during a conversion study from hep-
arin 10,000 U/ml to 4% citrate locks. The rate of
flow-related catheter exchange, tPA use, and bactere-
mia did not differ in the year of heparin locks com-
pared with the subsequent year of citrate locks with
over 30,000 catheter days at risk in each period. Un-
expectedly, a higher concentration of TSC (47%) pro-
duced a significantly higher catheter thrombosis rate
(measured by the use of a urokinase lock) versus stan-
dard heparin lock (43).
The antimicrobial activity of TSC is concentration
dependent (37), and higher concentrations would be
desirable. However, there is concern over using higher-
concentration TSC, and currently the Food and Drug Ad-
ministration (FDA) restricts tricitrosol in the United States
to ⬍4% (44). Questions remain regarding the optimal lock-
ing frequency and dose of any agent to optimize catheter
patency (45).
The American Society of Diagnostic and Interven-
tional Nephrology Clinical Practice Committee (46)
recommends using a locking solution of 1000 U/ml
heparin or 4% TSC to maintain TDC patency. The
need for tPA for maintaining catheter patency may be
increased by using 1000 U/ml heparin lock compared
with higher heparin concentrations, but safety consid-
erations mandate that higher concentrations of hepa-
rin lock be reserved for patients with evidence of
catheter occlusion or thrombosis after 1000 U/ml hep-
arin.
Managing Thrombotic Access Dysfunction with
Anticoagulants and Lytic Agents
Thrombus formation within or at the tip of an HD
catheter can be resolved by catheter replacement
alone, catheter replacement with balloon disruption
of the fibrin sheath, or stripping of the fibrin sheath
from a femoral vein approach (47). In a randomized
230 Clinical Journal of the American Society of Nephrology
clinical trial pilot study in 47 patients, 70% of whom
had sheaths, disruption of the sheath compared with
no disruption prolonged the median time till repeat
dysfunction from 97 to 373 days, modestly increased
mean blood flow, and produced a higher URR, 72%
versus 66% (48). The choice of technique should be
guided by factors including cost and patient and phy-
sician preference. Catheter replacement with sheath
disruption is invasive, inconvenient, costly, and time
consuming and increases patients’ risk for additional
complications, but in our opinion it produces more
durable results.
Prophylactic warfarin has shown some effect in
reducing thrombus formation rates in patients with a
TDC (49 –51). The importance of adequate systemic
anticoagulation (international normalized ratio, 1.5 to
2.0) is crucial (49). Malfunction-free catheter survival
at 9 months was 47.1% in patients with adequate
anticoagulation compared with 8.1% in patients with-
out (P ⫽ 0.01). However, the risk of bleeding and the
need for regular monitoring and possibly dose adjust-
ment makes this a less than ideal therapy for routine
use in HD (33). Moreover, use of warfarin in HD
patients has become controversial, because warfarin
may promote vascular calcification (52).
Of the commonly available antiplatelet agents, nei-
ther acetylsalicylic acid or dipyrimadole have shown
consistent efficacy in preventing TDC thrombosis.
Clodiprogel has not been systematically studied.
Noninvasive pharmacotherapy with lytics has
proved to be effective in restoring catheter patency,
and a number of lytic agents are currently available
(53). However, there are no thrombolytic agents ap-
proved for the clearance of occluded TDCs . Use of
lytics is on the basis of data of thrombus clearance
found in other smaller central venous catheters.
Safety issues with urokinase for this purpose led to its
withdrawal in the United States in 1999 (54). Both the
manufacturers and subsequently the FDA warned
that streptokinase should not be used for thrombo-
lytic clearance of indwelling catheters because of the
risk of allergic reaction and the frequency of serious
adverse events (55). By default tPA (alteplace) became
the only approved agent for thrombus clearance of
central venous catheters.
Alteplace
A variety of protocols are used by dialysis centers
to restore TDC blood flow. Frequently a lytic is used
as an intradialytic dwell of 1 hour when the Qb
achieved (⬍250 ml/min) would be unable to provide
adequate dialysis even after moderate extension of
treatment time. Two strategies attempt to improve Qb
before development of an “emergency” TDC flow
problem: so-called pre-emptive postdialysis lytic lock
or intradialysis lytic infusions. There have been no
comparative outcome studies of the various strate-
gies.
Short-term dwells should produce suboptimal re-
sults because diffusion of lytics to the site of occlusion
(thrombus or fibrin sheath) is limited, yet a 1-hour
dwell (repeated if the first instillation is unsuccessful)
has been the most common protocol studied. In some
protocols the lytic is slowly pushed in by injection of
saline 0.2 ml/lumen every 10 to 15 minutes to ad-
vance the lytic to the catheter tip during the 1-hour
dwell. This strategy decreased the need for repeat
lytic dwells by 81% while maintaining the proportion
of successful declottings (56).
In all of these instances, lytic use is intermittent and
conditioned by catheter performance at any moment
in time. The use of lytics as locking solutions between
all dialysis sessions has been recommended by
Gabutti et al. (57). Postdialysis lock with urokinase
versus conventional heparin (5000 U/lumen) was as-
sociated with increased Qb and reduced occurrence of
dysfunction.
If maximizing flow is the key issue, then the study
of Twardowski (58) has particular relevance; Twar-
dowski’s study sought to minimize the occurrence of
inadequate Qb (⬍400 ml/min during any dialysis
session). Locking the catheter with 5000 to 9000 U of
urokinase between treatments was successful in re-
storing flow in only three of 21 instances, whereas
infusion of 20,000 to 40,000 U of urokinase into the
catheter restored function in 10 of 25 instances. Even
when there was an inability to aspirate from the cath-
eter at all, infusion rather than locking was successful
in restoring the ability to dialyze with adequate blood
flow in eight of nine patients. Twardowski suggested
a “prophylactic” strategy for lytics. Whenever a non-
positional progressive deterioration of blood flow
was noted, 250,000 U of urokinase was infused during
dialysis over 3 hours, if there were no contraindica-
tions. Successful full restoration of Qb (⬎400 ml/min)
was achieved in 132 of 162 (81%) instances. In those
failing to achieve the desired Qb, repeat infusions
increased the success rate. Whether the increased cost
of intradialytic high-dose urokinase could be offset by
the high probability of positive results, saving on
transportation expenses and nursing and patient
time, and avoidance of catheter stripping or catheter
exchange was not formally studied.
The remaining discussion will focus on the recom-
binant tPA alteplase, reteplase, and tenecteplase (an
emerging thrombolytic agent).
Efficacy of Lytic Therapy in Catheter Clearance
Two studies have demonstrated efficacy for alte-
plase 1 mg/ml instillation in restoring the patency of
occluded HD catheters (59,60). A single instillation of
low-dose alteplase with a 30-minute dwell restored or
maintained Qb ⬎300 without line reversals in 36 of 50
(72%) patients, with a second instillation restoring
patency for a further four patients (40 of 50 patients;
80%) (59). The majority of patients (70%) required
additional intervention within the 4-month follow-up
of further alteplase instillation (62%; median time to
next exposure 14 days) and/or radiologic interven-
tion (59). The financial savings over replacement of
dysfunctional catheters in these 50 patients was esti-
mated at approximately 22,000 Canadian dollars. In
Clin J Am Soc Nephrol 6: 227–234, January, 2011
the second study, Qb of ⬎300 ml/min was completely
restored in 23 of 62 (37%) episodes of low Qb (⬍250
ml/min; mean pretreatment Qb, 130 ml/min; and
mean post-treatment Qb, 320 ml/min) (60). Partial
improvement (mean pre- to post-treatment Qb from
69 to 233 ml/min) was restored for 20 of 62 episodes.
Clearly the degree of flow restoration varied inversely
with the pretreatment blood flow. Nineteen episodes
failing to respond to alteplase installation therapy
were shown to have malposition or sheath formation
(60). Neither low-dose study systematically collected
safety data. In two other studies, a single instillation
of a higher dose (2 mg/ml) restored Qb to ⱖ200
ml/min in 15 of 18 episodes (83%; mean post-treat-
ment Qb, 260 ml/min) (61) and in 49 of 56 episodes
(88%; mean post-treatment Qb, 248 ml/min) among
22 patients (62). The mean flow rate in both of these
studies would be regarded as dysfunctional using
current guidelines (2), reflecting the previous ten-
dency to delay thrombolytic therapy until the dys-
functional process was very advanced.
Studies have shown alteplase more effective than
urokinase in restoring flow to occluded HD catheters
(62,63). Single dwell instillation (up to 60 minutes) of
low-dose (1 mg/ml) alteplase led to significantly
more patients achieving Qb ⬎300 ml/min than with
urokinase (5000 U/ml) (70% versus 35%; P ⫽ 0.013)
and completing an HD session (93% versus 70%; P ⫽
0.023) (63). The mean post-treatment Qb was 291 ml/
min in the alteplase group and 203 ml/min in the
urokinase group. Using a 30-minute push protocol,
alteplase restored Qb (⬎200 ml/min) in 92% of par-
tially occluded catheters (mean post-treatment Qb 260
ml/min) and 85% of completely occluded catheters
(mean post-treatment Qb 246 ml/min) (64). An anal-
ysis of 14 patients who had previously received uroki-
nase for catheter occlusion revealed that alteplase was
significantly more likely to partially restore the flow
(Qb ⬎200 ml/min) of completely occluded catheters,
88.2% versus 42.8% (64).
Optimal dwell times for lytics have yet to be for-
mally defined. Indeed, both short (1 hour) and long
(⬎48 hours) dwell times preserved catheter patency
for the subsequent HD session; patency was pre-
served for a mean of 14 days with both protocols (65).
The long-term patency rate after alteplase instillation
remains to be determined. In a 36-month follow-up of
570 HD catheters, the overall catheter half-life was 10.2
months, the median time from first to second alteplase
instillation was 27 days, and the period from second to
subsequent instillations was 10 to 18 days (66).
Alteplase infusion protocols also successfully re-
store HD catheter flow, even when associated with
fibrin sheaths (67,68). Administration of alteplase 2.5
mg per port over 3 hours resulted in a 91% success
rate (effortless aspiration and infusion capability
through both lumens) for the subsequent HD session,
but primary patency rates were relatively short (68).
Infusion of alteplase 2.5 mg/h/port over 2 hours
(total dose 10 mg) restored flow to ⬎250 ml/min in all
25 patients presenting with poorly functioning HD
Hemodialysis Catheter Flow, Besarab and Rahul 231
catheters; catheters remained patent to 30 days in 54%
of patients and to 45 days in 33% of patients (67).
Reteplase has demonstrated similar efficacy in re-
storing the flow of occluded HD catheters in two
retrospective analyses (69,70). Reteplase (0.4 U/lu-
men; dwell time, 30 minutes) restored/improved Qb
in 44 of 50 patients (69); 50 of 59 patients were able to
complete HD in another study (70).
These published studies of thrombolytics for the
treatment of HD catheter flow dysfunction have been
limited by small numbers of patients, differing dosing
regimens, lack of control data, and inconsistent defi-
nitions of treatment success (71), with success often
defined as flow rates that would be considered as
dysfunctional according to the current KDOQI guide-
lines (2,24). More recent studies with tenecteplase,
which has increased fibrin specificity, greater resis-
tance to plasminogen activator inhibitor-1, and a
longer half-life, have adopted more rigorous defini-
tions of treatment success (72,73).
Tenecteplase was evaluated in two large pivotal
studies: TROPICS (Tenecteplase for the Restoration of
Function in Dysfunctional HD Catheters) 3 (72) and 4
(73). In both trials, the KDOQI Qb criteria of ⬍300
ml/min and a flow of ⱖ25 ml/min less than pre-
scribed were used for inclusion. Acute therapy as well
as extended interdialytic dwell were evaluated on
TDC delivered blood flow in both studies. The pri-
mary efficacy end point was defined as Qb ⱖ300
ml/min and an absolute increase of ⱖ25 ml/min
from baseline after the 1 hour lytic dwell that per-
sisted at 30 minutes before and at the end of HD. If
both of the above criteria were not achieved, open
label tenecteplase, given as an extended intradialytic
dwell period (up to 72 hours), was evaluated.
An overnight extended dwell was more effective in
restoring adequate flow (⬎300 ml/min) than the short
dwells. Overall treatment success (Qb of ⬎300 ml/
min and increase by 25 ml/min) was achieved in 22%
of patients after single 1-hour dwell (no extended
dwell; TROPICS 3), 40% when the initial 1-hour dwell
was followed by extended dwell in TROPICS 3, and
49% when the initial dwell was followed by an inter-
dialytic dwell in TROPICS 4.
Delivery of Lytic Therapy as an Interdialytic
“Locking” Solution
Five studies suggest that use of tPA as a catheter
lock solution may effectively reduce the risk of vessel
occlusion between HD sessions with no increased risk
for bleeding events (74 –76). In a prospective, double-
blind study of alteplase versus heparin among nine
children, alteplase 1 mg/ml between HD sessions
significantly reduced the risk for clot formation (P ⫽
0.001) (76). In the following year, using interdialytic
tPA locks, a significant reduction in both the inci-
dence of blocked lines requiring tPA infusion (P ⬍
0.03) and the need for surgical replacement (P ⬍ 0.02)
was observed. In a separate study, a 2-mg tPA locking
solution preserved catheter performance between HD
sessions in 10 patients undergoing HD (75). Further
evaluation of lytic locking solutions is warranted .
232 Clinical Journal of the American Society of Nephrology
An observational study evaluated reteplase as an
interdialytic lock solution (77). The mean ⫾ SD dura-
tion of catheter patency was 45 ⫾ 39 days. Among 85
episodes of catheter dysfunction, higher reteplase
doses (4 to 6 U versus 1 U) were associated with a
higher but not statistically significant rate of restored
catheter function (91% versus 84%, respectively).
Unmet Needs and Unanswered Questions with Lytic
Therapy in Catheter Clearance
For patients with Qb ⬍250 ml/min, acute lytic ther-
apy offers a short-term solution to restore indwelling
catheter patency and allows a window of opportunity
to implement alternative HD delivery access (66), em-
phasizing the need to monitor patients to detect early
signs of occlusive dysfunction. Studies are needed in
this setting to determine the benefits, with regard to
long-term catheter patency, of early lytic intervention
on an individual basis using, for example, percentage
changes in Qb between HD sessions rather than a
defined Qb to trigger therapy.
Clinical studies are also needed to determine the
relative merits of the various approaches to lytic ther-
apy, particularly the value of prophylactic therapy
using an interdialytic locking solution between HD
sessions for prolonging catheter patency. The Pre-
CLOT (Prevention of Catheter Lumen Occlusion with
tPA versus heparin) study may help answer this ques-
tion (78). Patients will be randomized to tPA 1 mg per
lumen once per week, with 5000 U/ml heparin as a
catheter-locking solution for the remaining two ses-
sions or to the control arm receiving 5000 U/ml hep-
arin as a catheter-locking solution after each dialysis
session. The primary outcome is catheter malfunction
on the basis of mean blood flow parameters while on
HD, and a cost-effectiveness analysis is planned with
catheter maintenance using once weekly tPA versus
heparin locking solution.
Current and Future Perspectives
Catheters continue to be used acutely and long
term in a significant proportion of HD patients. HD
catheter care should routinely involve pre-emptive
surveillance for emerging access dysfunction (in
terms of declining Qb and delivered dialysis dose).
Early detection of a failing catheter should permit
prompt lytic therapy to salvage the indwelling cath-
eter, thereby avoiding or at least delaying the need for
catheter replacement. In patients with a need for fre-
quent lytic therapy, further thrombolysis may not be
as effective as sheath disruption. The evaluation of
combined antibiotic and antithrombotic locking solu-
tions in prolonging the life of TDCs is ongoing (79,80).
Catheters surface-treated with antithrombotic coat-
ings (81) appear to reduce platelet adhesion and
thrombus formation on the catheter. However, there
is an absence of clinical data confirming a reduction in
catheter-related complications (81).
Conclusions
Although catheters are not regarded as appropriate
for long-term HD delivery, they offer a number of
advantages in the acute setting, acting as a bridge to
more permanent vascular access, and are useful for
patients ineligible for arteriovenous fistula or arterio-
venous graft. Indeed, continued improvements in the
design and performance of catheters along with poor
access preparation before initiation of dialysis sug-
gests that they will continue to be the initial method
of access for the majority of patients initiating long-
term HD.
Attention to monitoring for dysfunction and infec-
tion, the two major clinical complications of catheter
use, as well as prompt intervention to salvage the
functionality of the indwelling catheter, are essential
in preventing or minimizing potential morbidity and
mortality. Lytic therapy to restore patency after
thrombus formation has proven effective. Future
studies should focus on evaluating prophylactic use
of lytics.
Acknowledgments
Support for some third-party writing assistance for this
manuscript was provided by Genentech, Inc. The content of
the manuscript was entirely within the control of the au-
thors.
Disclosures
Dr. Pandey has no disclosures. Dr. Besarab has been a
consultant to Genentech, Inc. in the past and has received
honoraria and consulting fees. He has lectured on thrombo-
lytic use and received honoraria from Roche, Canada.
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