Endovascular Treatment Options of Acute Limb Ischemia

doi:10.4236/ijmpcero.2013.21006

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International Journal of Medical Physics, Clinical Engineering and Radiation Oncology, 2013, 2, 39-43

Published Online February 2013 (http://www.scirp.org/journal/ijmpcero)

http://dx.doi.org/10.4236/ijmpcero.2013.21006

Endovascular Treatment Options of Acute Limb Ischemia

Di Zhang, Wensheng Lou, Guoping Chen, Xindao Yin, Jianping Gu

Department of Radiation Physics, Nanjing Hospital, Nanjing Medical University, Nanjing, China

Email: [email protected], [email protected]

Received October 14, 2012; revised November 15, 2012; accepted November 22, 2012

ABSTRACT

Acute limb ischemia is an urgent condition which occurs when there is an abrupt interruption of blood flow into an ex-

tremity usually because of either embolic or thrombotic vascular occlusion. Restoration of perfusion through early in-

tervention can decrease amputation and mortality. Contemporary treatment includes both surgery and endovascular te-

chniques. There is a rapid progress in endovascular intervention therapy. This article aims to make a comprehensive

review of the endovascular intervention options of acute limb ischemia.

Keywords: Acute Limb Ischemia; Arterial Embolus; Arterial Thrombosis; Endovascular Therapy

1. Introduction

Acute limb ischemia (ALI) of the lower extremities re-

mains a challenging clinical dilemma, which occurs when

there is an abrupt interruption of blood flow into an ex-

tremity usually because of either embolic or thrombotic

vascular occlusion [1,2]. The major clinical sign of ALI

is “6P”, i.e., pain, parasthesia, paralysis, pulselessness,

pallor and poikilothermia [3]. The overall prognosis is

poor, the mortality rate was 5.3% - 12%, amputation rate

was 5.3% - 14% [1,4-6]. When profound ischemia ensues,

this represents an emergency in which restoration of per-

fusion through early intervention can lead to limb sal-

vage, whereas delay may result in significant morbidity,

including limb loss and, potentially, death. Therefore,

timely and correctly treatment of this disease is impor-

tant.

There are three management options in acute lower

limb ischemia: 1) clot removal by catheter-directed thro-

mbolysis with or without percutaneous mechanical thro-

mbectomy; 2) surgical thromboembolectomy followed

by correction of underlying arterial lesions; and 3) anti-

coagulation with continued observation. We can catego-

rize the level of the patient’s limb ischemia utilizing cli-

nical assessment of motor and sensory function and in-

terrogating ankle arterial flow velocity signals into seve-

ral levels [7]. As shown in Table 1, those with level I

ischemia, particularly if they have significant comorbi-

dities, can and should be treated with heparin and ob-

servation, being watched closely while attention is given

to treating associated comorbidities. Conversely, in pa-

tients with the same level of ischemia (I), i.e., active pa-

tients without significant comorbidities, it is practical to

proceed directly with endovascular revascularization

(CDT and, possibly, percutaneous mechanical thrombec-

tomy). This same management choice is equally appro-

priate for those at level IIA, and at both of these levels of

ischemia there should be sufficient time for restoration of

patency using either endovascular or open surgical tech-

niques [8]. In the past, the decisional breakpoint in

choosing between endovascular and surgical revascu-

larization came between class IIA and class IIB, Treat-

ment of ALI has shifted toward endovascular therapies

because of rapidly improving technology and delivery

systems unless there is a contraindication, such as pro-

found critical limb ischemia, renal dysfunction, or con-

trast allergy. Regardless of which kind of therapy to be

chosen, the patient should be immediately anticoagu-

lated to prevent further clot extension. This article aims

to make a comprehensive review of the endovascular op-

tions with intra-arterial thrombolysis and/or adjuvant en-

dovascular techniques.

2. Catheter Directed Thrombolysis (CDT)

The development of effective medications to dissolve oc-

cluding thrombus led to the increasing use of throm-

bolytic therapy in patients with ALI. Randomized control

trials have provided a rationale for thrombolysis as a first

step in patients with ALI vs immediate operative revas-

cularization. Catheter directed thrombolysis offers seve-

ral potential advantages to lessen the pitfalls of open

techniques. By utilizing an endovascular approach and

local anesthesia, the risks of general anesthesia are mini-

mized within a subgroup of patients that are at their

physiologic limits [9]. In addition, enzymatic dissolution

of thrombus allows for more effective clot resolution

particularly within distal arterial beds that are often re-

D. ZHANG ET AL.

Table 1. Clinical categories of acute limb ischemia.

Category Prognosis Sensory Loss Motor Deficit Arterial

Doppler Venous

Doppler

I: Viable No immediate threat None None AudibleAudible

IIA: Marginally threatened Salvageable if promptly treated Minimal (toes) or none None InaudibleAudible

IIB: Immediately threatened Salvageable if immediately

revascularized More than toes, rest pain Mild/Moderate InaudibleAudible

III: Irreversible Major tissue loss, permanent nerve

damage inevitable

Profound,

anesthetic

Profound,

paralysis Inaudible Inaudible

sistant to open thrombectomy.

There are many evidences from randomized trials com-

paring catheter-directed thrombolysis with operative re-

vascularization. Ouriel et al. published a study that has

come to be known as the Rochester trial. The investiga-

tors randomized 114 patients with acute limb ischemia of

fewer than 7 days duration to urokinase or surgical in-

tervention. At 1 year, the cumulative risk of amputation

(18%) was identical in the two groups, while the cumula-

tive survival rate was significantly improved in patients

randomized to the thrombolysis group (84% vs 58% at

12 months, p = 0.01). The mortality differences seemed

to be primarily attributable to an increased frequency of

in-hospital cardiopulmonary complications in the opera-

tive treatment group (49% vs 16%, p = 0.001). The bene-

fits of thrombolysis were achieved without significant

differences in the duration of hospitalization (median 11

days) and with only modest increases in hospital cost in

the thrombolytic treatment arm (median $15,672 vs

$12,253, p = 0.02). Thrombolysis was equally effective

in those with embolic and thrombotic occlusions, al-

though the survival benefit was greater for patients with

embolic occlusions [10]. The Thrombolysis or Peripheral

Arterial Surgery (TOPAS) investigators randomized 213

patients with acute lower extremity ischemia secondary

to native arterial or bypass graft occlusion of fewer than

14 days duration to a variable dose of recombinant uro-

kinase (rUK) or surgery. Among patients treated with

rUK, surgical operations were avoided in 46% of patients

and the magnitude of such procedures was reduced in

50% of cases. Survival and amputation-free survival at

12 months were similar in the rUK and surgical groups.

Amputation-free survival was similar in the two groups.

There was a trend toward a higher amputation-free sur-

vival among those randomized to surgery and signifi-

cantly more bleeding in those randomized to rUK.

Among patients treated with rUK, thrombus resolution

and clinical outcome were somewhat better for acute

bypass graft thrombosis than for native arterial occlusion.

For thrombi longer than 30 cm, post-hoc analysis sug-

gested that 1-year amputation-free survival was better

following thrombolytic treatment, potentially due to lack

of suitable outflow for a surgical procedure. In contrast,

shorter occlusions fared better with surgery [11]. Al-

though The Surgery versus Thrombolysis for Ischemia of

the Lower Extremity (STILE) trial was prematurely ter-

minated by the Data and Safety Monitoring Board, sub-

sequent analysis, however, offered important insight. Pa-

tients presenting with acute ischemia (14 or fewer days)

and randomized to thrombolysis had significantly better

limb salvage (89% vs 70%) and amputation-free survival

[12].

It is very important to monitor coagulation parameters

carefully which aim to reduce risk hemorrhagic compli-

cations (estimated at 6% to 12.5%) during CDT proce-

dure [3,9-11]. Fibrinogen levels should also be checked

as a level < 100 mg/dL which reflects systemic fibrinoly-

sis and an increased risk of bleeding [12].

The severity of acute limb ischemia should be consi-

dered as the basis for therapic decision if we could use

CDT. CDT has long re-flow time, which can aggravate

ischemic. ALI of a limb artery can occur in the presence

or absence of underlying atherosclerotic involvement. If

there is no underlying atherosclerotic disease of the limb,

the thromboembolic event usually presents with pro-

foundly ischemic lower extremity, whereas thromboem-

bolic occlusion of chronically diseased lower limb artery

may present only with mild progression of chronic sym-

ptoms because of the development of collateral vessels

[8]. If ALI is located in the chronically diseased artery,

CDT could be the first choice.

We should master contraindications for CDT in ALI in

case of fatal haemorrhage [2,13]. Absolute contraindica-

tions to thrombolysis are well-known and include active

bleeding, central nervous system injury, or major opera-

tive procedures within the preceding 2 weeks. Relative

contraindications include uncontrolled hypertension, re-

cent eye surgery, pregnancy, and intracranial neoplasms.

3. Percutaneous Mechanical Thrombectomy

(PMT)

CDT is associated with slow restoration of blood flow,

which may aggravate tissue damage. The advent of PMT

has allowed removing clot burden quickly with CDT bol-

stered by using of PMT devices and can be used in pa-

D. ZHANG ET AL. 41

tients with acute profoundly limb ischemia. The earlier

clot-removing methods are applied, the better the out-

comes. Although no randomized prospective study showed

that safety and efficacy of percutaneous mechanical thro-

mbectomy or combined with thrombolysis in the treat-

ment of ALI, some data has shown its advantage in fast-

reflow and improvement of patients’ symptoms, and

PMT may be the only available treatment option in pa-

tients at high risk for open surgery or with contraindica-

tions to pharmacologic thrombolysis. K. Kasirajan et al.

published that thrombus removal rate was 85%, using a

PMT catheter as an initial treatment for acute (<2 weeks)

and subacute (2 weeks to 4 months) arterial occlusion of

the limbs. Angiographic outcome was not dependent on

the duration of occlusion or the conduit type [14]. Ansel

GM and his colleagues showed results of treatment of

acute limb ischemia with a percutaneous mechanical thro-

mbectomy-based endovascular approach. Angiography

following PMT showed thrombus removal complete/

substantial 63.6%, partial 28.0%, and minimal 8.8%, res-

pectively, and amputation free survival of acute limb is-

chemia treated with PMT alone or in combination with

thrombolysis was 94.7% at five-year follow-up [15].

Oguzkurt L et al. reported that complete thrombus re-

moval with PMT was achieved in 90% with acute occlu-

sions. Amputation-free survival rate was 100% at one

month, 93% at one year, and 93% at two years [16].

There is a new effective method to dissolve occluding

thrombus reported recently which using isolated phar-

maco-mechanical thrombolysis-thrombectomy (IPMT) to

isolate the thrombus between two balloons and utilize

wire oscillation to increase the thombus-lytic exposure

surface area followed by aspiration. IPMT decreases sys-

temic lytic exposure, procedure time, and distal embo-

lism [17].

PMT has generally been used as an adjunctive method

to CDT, but reverse was also true, and CDT could be an

adjunctive to PMT. Total dose of thrombolytic drug used

was low because PMT removed most of the thrombi in

most cases [14,15]. Main disadvantages of PMT were the

need for larger vascular sheath for large guiding catheter

than usual and the dissection of the artery. It should be

noted that a patient’s symptoms may get transiently wor-

se as the thrombus fragments with distal emboli. Distal

embolisation has been reported in 10% of cases with the

PMT procedure [16]. So during PMT, the operator should

perform gently to reduce risk of distal embolisation and

vascular injury.

4. Angioplasty

Successful clot dissolution will unveil a “culprit” lesion

responsible for initiating thrombosis. Angioplasty is not

the preferred initial method of treatment for ALI, only in

patients considered unfit for thrombolysis or in patients

who had undergone unsuccessful surgical recanalisation

or treatment with residual stenosis, as well as dealing

with intraoperative complications remedies [18]. Arte-

riography following removal of the thrombus by throm-

bolysis, and/or PMT usually delineates the responsible

lesion and, a decision must then be made in regard to

how best to manage this lesion and eliminate the threat of

recurrence it poses. Discrete atherosclerotic lesions are

well managed by either balloon angioplasty or, if acces-

sible in the surgical field, by surgical revision with patch

angioplasty, both yielding durable results. However,

longer, more extensive lesions or multiple stenoses-in-

series are still best treated by bypass. Kashyap et al. re-

ported in an overwhelming majority of cases (91%), an

adjuvant procedure was performed to treat the “culprit

lesion” leading to thrombosis. This was a purely percu-

taneous endovascular procedure in 56%, an open surgical

procedure in 15% and a combined approach in 28% [4].

Plate et al. [19] reported that angioplasty ratio after CDT

and/or PMT was 68%; PTA was 60%, 5% stent implan-

tation, aneurysm exclusion 2%, and 1% endarterectomy.

Kim et al. reported 15 cases of ALI underwent stent im-

plantation, technical success rate was 100%. Duration of

the intervention ranged between 20 min and 50 min.

During the average follow-up of 14.4 months, no re-oc-

clusion or restenosis was observed by CT angiography or

duplex USG [18]. Oguzkurt et al. [16] reported using

long-duration balloon inflation with/ without stent place-

ment to fix artery dissection. The articles about stenting

in ALI gradual increase in recent years, with good clini-

cal efficacy and no occurrence of distal embolization [20,

21]. Stent-assisted recanalisation may be an effective

treatment for patients with acute limb ischaemia who are

considered unfit for thrombolysis or surgical recanalisa-

tion or who have severe ischaemia requiring immediate

recanalisation or occlusion in the iliac arteries. Berczi et

al. [22] treated seven acute thrombotic occlusions in the

iliac arteries by primary stent implantation without distal

embolisation.

5. Embolic Protection Devices (EPDs)

Distal embolization following percutaneous revasculari-

zation procedures is a universal phenomenon that has

been reported in various vascular beds, including the ca-

rotid and renal arteries and the lower extremities. Distal

embolization may make it necessitate the use of addi-

tional interventions, including thrombectomy or throm-

bolysis, resulting in longer procedure time, greater

amount of contrast used, and larger radiation exposure.

EPDs are considered as a ‘‘standard of care’’ during per-

cutaneous carotid interventions, coronary artery bypass

graft PCI, and even renal angioplasty based on recent da-

ta. Although the FDA has not ratified any EPDs for pe-

ripheral arterial, several works have shown the safety and

D. ZHANG ET AL.

feasibility of EPDs use in this vascular territory. There

was a report, the first time in 2003, about using EPDs in

peripheral vascular angioplasty, and filter membranes

were evaluated with scanning electron microscopy. Sys-

tem delivery was successful in all patients [23]. D. Siab-

lis et al. [24] investigated the feasibility, safety and distal

emboli protection capability during recanalization of

lower extremities’ acute and subacute occlusions. Tech-

nical success rate of deployment and utilization of the

filtration devices was 100%. Macroscopic particulate de-

bris was extracted from all the filters containing fresh

thrombus, calcification minerals, cholesterol and fibrin.

Shammas et al. [25] reported that there were no compli-

cations related to the release and recovery process of the

device. Although many researchers believe patients with

high risk for distal embolic, poor outflow tract and direct

plaque excision will derive the greatest benefit from the

use of this technology, large multicenter registry is need-

ed to define the exact effects for these devices, to im-

prove the technical design for this unique vascular bed,

and clearly to identify best indications [23-25].

6. Summary

The treatment methods chosen should be based on the

patient’s conditions and angiographic results during cli-

nical practice. Now more and more interventional thera-

pies for ALI which derive from combinations of several

procedures above are used to restore blood flow quickly

and reduce complications. CDT combined with PMT

plus PTA/stent for ALI can be effective and minimally

invasive. In the future, one can expect to improve endo-

vascular techniques to the point where it will more sig-

nificantly impact on the management of acute as well as

chronic lower extremity occlusive diseases.

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