Interventional Karim

Valji,

MD

Joseph

#{149}

J.

Bookstein,

MD

Anne

#{149}

C. Roberts,

MD

Gary

Radiology

B. Davis,

#{149}

MD

Pharmacomechanical Thrombolysis and Angioplasty in the Management of Clotted Hemodialysis Grafts: Early and Late Clinical Results’ The results of pharmacomechanical thrombolysis and angioplasty of 121 thrombosed hemodialysis grafts were reviewed. The initial pharmacomechanical method (used in 65 cases) employed clot maceration with hook-shaped catheters and clot lacing with highly concentrated urokinase. The current technique (used in 56 cases) consisted of pulsed-spray injection of urokinase into the clot. All fully treated grafts (117 cases) underwent complete or near-complete thrombolysis, and 93% remained patent after 1 day. Mean time for pulsed-spray lysis was 46 minutes ± 21. One patient (less than 1%) had gastrointestinal bleeding and received a transfusion; minor complications occurred in 3% of patients. Primary and secondary graft patency rates for both methods at 1 year were 26% and 51%, respectively. While graft age and results of angioplasty did not influence future graft patency, shorter intervals between graft thromboses was predictive of earlier subsequent graft failure. Results suggest that pharmacomechanical thrombolysis and angioplasty provide rapid, consistent, and safe recanalization of clotted hemodialysis grafts and represent a promising additional therapeutic approach to long-term graft management. Index terms: plasty, 91.128 interventional sis, 91.1274 luminal

Radiology

I

From

Arteries, #{149} Dialysis, procedure, #{149} Urokinase,

angioplasty,

91.128

1991;

the

transluminal angioshunts, 91.44 #{149} Grafts, 91.128 #{149} Thromboly91.1274 #{149} Veins, trans-

nal

revision

received

of Radiology

July

requests

transluminal

have been vestigators hernodialysis However, lytic

10; accepted

to Ky.

agents

into

these

grafts

has

been

hampered by prolonged treatment times, incomplete clot dissolution in a large number of cases, and significant bleeding complications. Largely on the basis of laboratory experiments demonstrating increased speed and consistency of fibrinolysis with use of direct admixture of urokinase (UK) with in vivo (6), we

clots in vitro (5) and developed techniques

of pharmacornechanical thrombolysis for treating thrombosed native antemies, arterial bypass, and vascular access grafts. We have reported the early clinical results of two versions of this method (7,8). The present study was designed to examine (a) the technical success and safety of these methods in the treatment of thrornbosed dialysis grafts from our large experience to date and (b) the longterm results of the procedure in prolonging graft patency.

18.

term

follow-up.

patent

Grafts

if they

ysis

without

ure

(eg,

sumes,

increasing

at dial-

of impending

elevated

graft

analyzed

by the

standard

errors

life-table

of graft were

SUBJECTS

AND

Seventy-three 121 thrombosed

METHODS

patients hemodialysis

with

was

method

of

grafts were referred for therapy to the vascular radiology services at the Univemsity of California, San Diego, and the La

Jolla Veterans Center tembem medical

Administration

Medical

between December 1989. We reviewed records, hemodialysis

1984 and Septhe hospital unit me-

angiography mefollow-up ended Data collection in-

underlying

graft,

inflow

normalities,

the

percentage

ametem after angioplasty the adjacent

TLA (luminal site compared normal vessel),

tions,

and

immediate

or outflow

results

ab-

luminal

of the

patency

computed

at various

by

the

of

assessment graft age, an-

gioplasty results, or the interval since previous therapy and the time to subsequent graft thrombosis was performed with

the

Two

Speamman

rank

methods

thrombolysis study period,

were both

previously

correlation.

of phammacomechanical employed of which

described

during the have been

(7,8,11).

In

both

techniques, two 5-F dilators are placed into the midportion of the graft in a crisscross fashion to obtain access to the entire clot

and

outflow.

the

The

technique,

initial

macerafion,

lacing/ bem

to evaluate

1984

was

inflow

from

1988.

North

mL)

injected which

was

catheters,

drawn

Ill;

the clotted UK

graft,

throughout

arterial

per

throm-

100,000meposi-

anastomosis

catheter

achieved. A pulsed-spray since

the

1988

method

holes

and

of choice

were

punched

catheters number

until

and

lysis

technique

January

IU/

thereby

the

midportion of the graft, infusions (4,000 IU/mL) were then started lU/mm

Labo-

25,000

through hook-shaped were rotated and with-

through

at the

con-

Abbott

Chicago,

distributing

Decem-

Highly

UK (Abbokinase;

matories,

and

termed

used

to February

centrated

graft

of UK at 2,000 was

has been continues

(8,11). into

with

a 27-gauge

of holes

was

used

to be

Multiple

tapered

needle.

determined

side 5-F

The by

the

length of clot the catheter would span. The dilators were exchanged for the themapeutic catheters, the end holes occluded with beaded wires (Cook, Bloomington, md),

and

static

Y adaptors.

the

catheters

fitted

Small

volumes

with

hemo-

(0.2 mL)

at the

that

of

complica-

and

in-

method

di-

diameter

with

(9);

estimates

Peto et al (10). Nonparametric of the correlation between

tioned

a total access

pres-

percent-

patency

of the

fail-

venous

recirculation

age). Cumulative

probability

considered

functional

evidence

markedly

tervals

were

remained

bus. The total lacing dose was 150,000 IU. With the catheters

cluded patient age, graft age and type, dose of UK given, the technique of and time for thrombolysis, the nature of the

H-756,

July

and (TLA)

used by a number of inin the treatment of failed access grafts (1-4). local infusion of fibrino-

angiograms, and ports of these patients; on December 31, 1989.

UCSD Medical Center, 225 Dickinson St. San Diego. CA 92103; and the Veterans Administration Medical Center, La Jolla, Calif. Received March 9, 1990; revision requested April 30; fiAddress reprint C RSNA 1991

thrombolysis angioplasty

RANSCATHETER

cords,

178:243-247

Department

T

long-

Abbreviations: ene, TLA urokinase.

=

PTFE transluminal

=

polytetrafluoroethylangioplasty, UK

243

of highly

concentrated

IU/mL)

were

tuberculin was

A fine,

created

UK through

that

the

given

distributed

a period

150,000 of

(approximately

two

ute).

The

of injections

to about

one

No intercurrent Lysis pation pulse

mm-

pulses

pulse

per

mm-

was

per

UK infusion

then

minute.

was given.

was monitored periodically by palof the graft for the presence of a and by injecting small amounts of

contrast

material

directly

side holes of the sis was recorded

or 100-mm graft appeared

thrombus, remained

or only within

was performed, jected through arterial

through

therapeutic with digital

techniques When the

the

U

15-20

utes reduced

a

high-pressure

About

frequency

with

rapidly

clot.

over

(25,000

injected

syringe.

spray were

urokinase

forcefully

spot

flow

scattered the graft,

3-4 mm angiography

anastomosis

sought

to document

and intragraft,

were

the

thrombolysis. abnormality

usually and

treated

tients were given mm intravenously therapy and were until

of clots

with contrast material ina dilator positioned near

stenoses

U/h

Ly-

radiographs. entirely free

complete or near-complete An underlying anatomic was then Anastomotic,

the

catheter. subtraction

found. venous

with

5,000-7,000 from the maintained

completion

out-

TLA.

Pa-

U of hepaonset of UK on 1,000 of angioplasty.

Coagulation parameters and fibrmnogen levels were generally not monitored because of the short duration of therapy. The entire procedure single session in the and

patients

home an

were

or to the

hour

discharged

dialysis

patients

hours local

prior bleeding.

within

Rarely,

compression to achieve

sites was in such

observed

to discharge

half

prolonged

of puncture hemostasis;

were

in a suite,

to their

unit

of completion.

digital required

cases,

was performed angiography

for

for

1-2

signs

the

121

cases,

a full

graft

could

not

en, contrast was

be entered;

material

noted

from

course

or a

in anoth-

extravasation

the

venous

anasto-

mosis before fibninolytic therapy was started. In a third patient, extravasation developed during UK treatment, and in a fourth patient, a large pengraft hematoma was noted during UK injection and the procedure was stopped. Among the 1 17 evaluable cases, the

average

patient

(range,

age

was

deviation).

three tulas

age

11-80

years).

14.6

months

was The

mean

± 18.6

graft

(standard

grafts

were

composed

panded

polytetrafluoroethylene

(PTFE).

Grafts (straight

forearm

Radiology

#{149}

were

located on loop

of fisall of

ex-

in the configura-

grafts

were

in

treated

within 3 days, and usually within 1-2 days, of thrombosis. Initial results of thrombolysis with use of the two phanmacomechanical techniques are summarized in Table 1 . Except for the four cases described above in which UK treatment was not begun or completed, complete or near-complete clot lysis occurred in

every case. Of these (7%) rethrombosed treatment

117 grafts,

In

ascertained:

five

cases

spasm. mediate

plained. The

and

injury

to venous

failure

underlying

thrombosis

are

was

causes indicated

Angioplasty was required cases to correct stenoses graft

patency.

were

presumably

cause

hepanin inability anastomotic to undergo

TLA from profound In the other three graft

Intragraft caused

after of the

the

insufficient

therapy, graft infection, cross a critical venous stenosis, patient refusal

TLA,

eight

immediately 24 hours

on within

procedure.

during

years

With the exception endogenous arteniovenous and one bovine heterograft,

access

244

47.6

In all cases,

cases.

RESULTS Among

90 cases, in the upper arm and in the thigh in three

in

24 cases,

of

of UK treatment was not begun completed in four. In one patient

tion)

was

thetic

dialysis

another

to

outflow

graft.

50,000

cessfully

mal

pseudoaneurysm graft

in

104 maintain

and stenoses by

neointi-

of

with

hyperplasia,

unex-

Table

pulsed-spray

UK.

The

plug

and

these

2.

responsible

require

immediate

a rounded, observed

for

on

filling

the

rial anastomosis complete fects

clot were

did

graft

repair.

focal

side

lysis

(Fig

not

failure on In 21 cases,

defect

graft

following

relatively

suc-

lesions ofballoon of graft

identified

appear

was

angioplasty.

yielded to high-pressure dilation. Three of five cases ten

for

IU

treated

venocases, im-

in

After

thrombolysis with 250,000 IU of UK and angioplasty of the venous anastomosis, the graft is widely patent with the exception of a focal filling defect on the graft side of the arterial anastomosis (arrow). Minimal additional lysis was noted after pulse injection of

was

of the

ante-

otherwise 1). These

resistent

deto

January

fur-

1991

fraction

of

grafts

---

patent

1

fraction it--

0.9

0.9

0.8

0.8

of grafts

patent

-

(59)

0.7

0.6

-

(70)

0.7

(eo)

0.6L

I

I

‘5 (53)

0.5

146)

0.5

j\

1--,-

0.3

.

(21)

-

(13)

(10) (13)

(11)

(10)

ri

0.3

I

U-j

I

-

0.4

(35)

(18)

(20)

I (43) 0.4

1

0.2

::F

(2)

6

(2)

(2)

0.1

12

-

0 30

24 months

after

36

0

6

12

thrombolysis

18

months

after

24 initial

30

36

thrombolysis

3. Figures

2, 3.

(2) Life-table

hemodialysis grafts. points. (3) Life-table thrombolysis. points.

analysis

Numbers analysis

Numbers

of primary

in parentheses of secondary

in parentheses

denote

angiogmaphy for to this manipula-

Fifty-six grafts were treated only once. Thrombolysis was performed twice in 19 grafts, three times in three grafts, four times in two grafts, and six times in one graft before surgical revision or replacement was mequired. At the time of repeat thrombolysis,

stenoses

were

identified

at

the venous anastomosis (67%), at the arterial anastornosis (19%), at the yenous .

outflow

(3%),

and/on

in the

graft (8%); in 19% of cases, no anatornic cause for repeated failure was found. In eight patients, rising yenous pressures during dialysis, weeks to months after thrombolysis, prompted angiography and TLA of the venous anastomosis to maintain graft function. The 109 technically successful cases (patent beyond 24 hours) were studied by life-table analysis for both primary (Fig 2) and secondary (Fig 3) patency rates. Primary patency is defined as the interval between the thrombolytic procedure and subsequent graft failure. Secondary patency is defined as the interval between the first thnornbolytic procedure for a particular graft and any surgical procedume required to restore vascular access (revision or replacement), allowing for intercurrent percutaneous Volume

178

Number

#{149}

1

mates

after

technically

successful

pharrnacomechanical

thmornbolysis

denote grafts at risk for each time interval. Standard errors are indicated patency mates of 81 dialysis grafts treated with single or repeated sessions

them thrombolytic therapy and TLA. Occasionally, a balloon occlusion catheter was used to gently dislodge these foci. While two patients noted transient, localized chest pain during the procedure, none of the patients required ventilation-perfusion scanning or pulmonary symptoms referable tion.

patency

grafts

at risk

for

each

time

interval.

Standard

errors

are

indicated

of 109 clotted

by vertical bars at data of phamrnacornechanical

by vertical

bars

at data

(TLA or repeat thrombolwho died (n = 8), underwent renal transplantation (n = 2), were placed on penitoneal dialysis (n 1), or were lost to follow-up (n

cases (graft extravasation and a pengraft hematoma) prevented completion of UK therapy, as noted earlier. graft

following

6) were considered withdrawn from the study at such time; grafts were patent at the time of exclusion in all of these cases. The primary patency rate following transcatheter therapy demonstrated a sharp decline after 1 month, to 68%. Thereafter, a slower drop-off was noted, with a 1-year patency of 26%. The secondary patency mate at 1 year, reflecting management of mepeated episodes of graft failure with

nous

stenosis.

procedures ysis). Patients

tmanscatheter relationships

therapy, between

was 51%. The graft patency

and graft age (when known), angioplasty results (percentage luminal diameter) at the venous anastomosis or outflow (when nadiognaphs were available for review and technically adequate for measurement), and interval since prior thrombolysis are plotted in Figures 4, 5, and 6, mespectively.

There

was

no

correlation

be-

tween percentage luminal diameter after TLA or graft age and subsequent graft patency. However, a highly significant correlation was found between the initial interval since therapy and the time to subsequent graft thrombosis (P < .001). One major complication occurred in a patient who testinal bleeding

proved

nodular

successful

a single-unit

developed gastroindue to endoscopy-

gastritis

thrombolysis.

blood

nor complications (3%) of the 121

1 day He

after

received

transfusion.

Mi-

were seen cases referred.

in four Two

Extravasation

in one

angioplasty

of a ye-

Clot

distal radial one patient; cessfully

was observed embolized

to the

and digital arteries these emboli were

treated

with

local

in suc-

UK

infusion. DISCUSSION our

The results previous

of this reports

study that

confirm pharmaco-

mechanical thrombolysis is very successful in restoring function to clotted hemodialysis grafts. Thrombolysis

is achieved

consistently,

rapidly,

and safely. In all clotted grafts treated with a full course of UK (97%), clots were lysed completely or nearly completely; 93% of these remained patent at 24 hours. The mean time for complete clot dissolution with the pulsed-spray method was 46 minutes, which is about half the time required with the lacing/macenation technique and at a somewhat lower average dose of UK (Table 1). The entire procedure is usually completed in about 2 hours. We believe that systemic fibrinogen depletion and the ensuing risk of hemorrhage are minimized by intrathnombic

deposition

of UK,

allows use of lower UK doses are commonly required with sion

served tion

techniques.

bleeding at recent

We

which

than infu-

infrequently

or hematoma dialysis

puncture

catheter insertion sites, contrary observations of other investigators Radiology

ob-

fommaor

to

245

#{149}

graft

patency

(mo.)

27

-

---

-

.

---

graft 2 1 r

__i

patency

(ma.) --__________

24 21

.

15

18

I

i5F

12.

-

60 graft

age

:

84

5.

4-6. Scatter plots of the relationship after phanmacomechanical thrombolysis and Figures

diameter

after

angioplasty

at the

between

from

the

plot

for

subsequent

graft patency

graft age (4), venous anastomosis

percentage or out-

flow (in 44 evaluable cases) (5), and interval since last thrombolytic therapy (6). In 6, two patients, with 34 and 40 months since last themapy and subsequent patency for 26 and 12 months, respectively, are excluded

i 60 % luminal

(ma.)

4.

luminal

_L

.

graft

diameter

patency

----------

21

the

______-

15L

clarity.

procedure.

Radiology

#{149}

9

.

r-

6-

.

3L

.

.--------------

Thus,

patients may be safely discharged home or to dialysis soon after therapy. The risk of clot ernbolization may be increased with mechanical thrombolysis. Two patients noted brief episodes of chest pain during the procedure, which could have represented venous embolization; arterial emboli developed in one case and were easily managed with further UK therapy. Increasing the pressure on rate of UK pulse injections beyond the current levels may be limited by this increasing risk of clot migration. Despite the unequivocal immediate success of our technique, the long-term function of treated grafts may ultimately determine the role of transcatheter therapy in dialysis graft management. While the 1-year primary patency rate of 26% seems discouraging, repeated transcatheter procedures enabled a 1-year secondary patency rate of 51%. This figure can be compared to the 1-year secondary patency nate of surgically mevised PTFE grafts of about 60%-70% (12,13). Palder and his colleagues noted that about 60% of revised grafts required at least one secondary procedure to restore patency (13). We advocate pulsed-spray thrombolysis for the first episode of thrornbosis of every dialysis graft, unless a 246

100

18

(3). Excessive heparinization was probably responsible for the gastrointestinal hemorrhage that occurred in one patient. With the exception of this single case, no episodes of delayed perigraft or remote bleeding after

80

angioplasty

(ma.)

12-

occurred

after

0

6

3 interval

since

last

9 thrombolysis

12

(mo.)

6.

contraindication ists (suspected

to the procedure exgraft infection, contra-

indication to anticoagulation/fibrinolytic therapy, or severe allergy to contrast material). About one-fourth of recanalized grafts will remain patent for over 1 year without further intervention.

Another

group

of pa-

tients will benefit from repeat transcatheter procedures to maintain function for more than 1 year. We attempted to identify factors that might help in predicting early graft meclotting in order to guide longterm management: (a) The length of initial interval of response to thrombolytic therapy correlated significantly with the length of subsequent intervals of response. Shorter intervals between graft thromboses predicted earlier subsequent graft failure. (b) Graft age did not correlate with the time to subsequent graft thrombosis. (c) Recurrent anastornotic narrowing from intimal hyperplasia depended on individual patient factors unrelated to residual stenosis after TLA. Evaluable images of yenous anastornotic and outflow stenoses after angioplasty (which were mesponsible for graft failure alone or in

combination

with

other

87%

were

available

of cases)

causes

in in 43%

of

cases. Surprisingly, the post-TLA percentage luminal diameter was not predictive of future graft patency. The wide distribution in vessel patency after angioplasty (Fig 5) meflects the occasionally high resistance of intimal hypemplasia to TLA despite the use of high-pressure balloons and multiple, prolonged inflations. The causes of graft failure were similar

in distribution

many other We identified thrombosis cess

of some

to that

reported series an anatomic in 92% of cases, surgical

in

(12,14). cause for far in ex-

series,

which

describe a 40%-50% prevalence of unexplained graft failure at the time of thrombectomy (13,15). In particular, arterial anastornotic stenoses warranting treatment were mon in our experience ously described.

The

“plugs”

rial anastomosis 18% of cases

remaining are

more than

cornprevi-

at the

arte-

after thmornbolysis problematic. Ether-

in

edge and his colleagues noted this finding commonly during surgical thrombectomy, with the Fogarty catheter yielding a whitish segment January

1991

of clot with The nature but

we

postulate

that

platelet-rich

formed

exposure

flow; this theory relative resistance agents. We transcatheter

are

might explain to thrombolytic

thmombosed

injections liminary

the

in

the

combination of thrombolysis is a promising methmanagement of

dialysis

cedure

is rapid

always graft.

effective The cost

grafts.

and

safe

and

The

pro-

almost

in recanalizing the and patient discomfort

associated with repeated surgical visions are avoided. Grafts may immediately

after

mebe

injection. other it the plasia ble for nally,

term

1.

patency therapy

3.

long

as possible,

pharmacomechani-

successful

means,

through

percutaneous

angiography

following

bolysis allows complete tion from the arterial tnal venous drainage,

surgical

throm-

graft evaluasupply to centhus guiding

therapy.

Schilling JT, Neff Dis

Number

#{149}

1

AJR

8.

hand

of athemectomy on devices may limof intimal hyperthat is nesponsiof graft failure. Fiis actively

phanmacolimit nestenosis improve long-

9.

10.

11.

JJ,

Eiser

MS.

AR,

The

Slifkin

role

access 1987;

RF,

Whitney

12.

of thrombolysis

occlusion.

in J Kid-

Am

10:92-97.

Young AT, Hunter DW, Castaneda-Zuniga WR, et al. Thrombosed synthetic hemodialysis access fistulas: failure of fibrino-

14.

154:353-356.

4.

5.

therapy.

Radiology

6.

1985;

154:639-

642. Rodkin RS, Bookstein JJ, Heeney DJ, Davis GB. Streptokinase and transluminal angioplasty in the treatment of acutely thrombosed hemodialysis access fistulas. Radiology 1983; 149:425-428. Bookstein JJ, Saldinger E. Accelerated thrombolysis:

in vitro

evaluation

of

with and

tissue-type

results

plasminogen Invest

activator:

of subacute Radiol

angioplasty.

thrombolysis.

In:

Castan-

1983;

94:464-470.

Palder SB, Kirkman RL, Whittemore AD, Hakim RM, Lazarus JM, Tilney NL. Vascular access for hemodialysis: patency rates and results of revision. Ann Surg 1985; 202:235-239. Puckett JW, Lindsay SF. Midgraft curettage as a routine adjunct to salvage operation for thrombosed polytetrafluoroethylene hemodialysis access grafts. Am J Surg 1988;

15.

and

eda-Zuniga WR. Maynar M, eds. Percutaneous revascularization techniques. New York: Thieme (in press). Etheredge EE, Haid SD, Maeser MN, Sicard GA, Anderson CB. Salvage operations for malfunctioning polytetrafluoroethylene hemodialysis access grafts. Sur-

156:139-143.

Rizzuti RP, Hale JC, Burkart TE. Extended patency of expanded polytetrafluoroethylene grafts for vascular access using optimal configuration and revisions. Surg Gynecol

agents and methods of administration. vest Radiol 1985; 20:731-735. Valji K, Bookstein JJ. Fibrinolysis intrathrombic injection of urokinase model

maceration 149:177-181.

Bookstein JJ, Fellmeth BF, Roberts AC, Valji K, Davis GB, Machado T. Pulsedspray pharmacomechanical thrombolysis: preliminary clinical results. AIR 1989; 152:1097-1100. Lee ET. Statistical methods for survival data analysis. Belmont, Calif: Lifetime Learning Publications, 1980; 88-95. Peto R, Pike MC, Armitage P. et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 1977; 35:1-39. Valji K, Bookstein JJ. Pulsed-spray phar-

gery

13.

lytic

clot 1987;

macomechanical

ag-

thrombosis.

178

over

GB, Dowd CF. Bookstein JJ, Maroney TP, Lang EV, Halasz N. Thrombosed dialysis grafts: efficacy of intrathrombic deposition of concentrated uro-

Davis

kinase,

preac-

Zeit RM, Cope C. Failed hemodialysis shunts: one year of experience with gressive treatment. Radiology 1985;

in a new

Volume

tested; further

#{149}

results.

ney

revision. In order to preserve limited vascular access sites as

cal thrombolysis serves as a useful adjunct to surgical therapy. When definitive therapy is not possible on un-

the

of UK

of thnombolysis

hemodialysis

2.

erative these

increase

References

treatment,

transcathetem the results of op-

may

penetration

involved in identifying logic agents that may after angioplasty and

avoiding placement of temporary subclavian vein access catheters that often damage the outflow from futune dialysis graft sites. Long-term with repeated approaches

that

and

The use recanalization progression at anastomoses most cases our laboratory

7.

meth-

A mechanical

is now being results suggest

celeration

planning to perform biopsy of these plugs

selected cases. In summary, pharmacomechanical and angioplasty od for long-term

injector

homogeneity

in-

in the

are underway.

pulse

a

from

to arterial

refinements

odology

it represents

thmombus

continuous

used

Further

a concave surface (12). of this defect is unknown,

Obstet

1988;

166:23-27.

In-

venous 1987;

22:23-27.

Radiology

247

#{149}