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74 Interventional radiology and endovascular procedures
Discussion
Infrapopliteal PAOD is a leading cause of CLI (Rutherford–Becker categories 4–6), a
limb-threatening situation that may result in major amputation, especially if revascularization attempts fail [6]. Balloon angioplasty is considered as the main percutaneous method for the treatment of BTK disease, and has technical success rates between
80% and 100% and two-year limb salvage rates of up to 80% depending on the degree
of infrapopliteal disease. Stenting is usually reserved as a bail-out option following
suboptimal or complicated angioplasty [7,8]. However, the introduction of drug-eluting
stents (DES) has transformed modern endovascular treatment protocols and provided
excellent clinical and angiographic outcomes [4,9]. As initial reports from single-centre series provided sufcient data supporting the mid-term safety and effectiveness
of infrapopliteal DES, larger multicentre randomized controlled trials (RCTs) were
conducted in order to compare DES with balloon angioplasty and bare metal stents
(BMSs) in the treatment of BTK arterial disease. Three recently published large-scale
randomized trials have provided level A scientic evidence for the angiographic and
clinical superiority of DES versus both angioplasty and BMS, supporting the primary
use of olimus-eluting stents for infrapopliteal lesions up to 90mm [10]. In this case the
decision to perform direct drug-eluting stenting was based on the superior primary
patency rates and target lesion re-intervention free interval and composite clinical
endpoints reported following the deployment of sirolimus-eluting stents compared
with angioplasty and/or BMSs. Another valid decision would be to carry out balloon angioplasty rst using a low-prole new generation dedicated infrapopliteal balloon catheter 3 × 100mm, and then perform bail-out stenting using DESs if necessary.
Indeed, although balloon angioplasty can be still considered as an effective treatment
of CLI, especially in long infrapopliteal lesions, as it is low cost, can be repeated with
relative safety, does not preclude any future surgical treatment, and results in high
long-term limb-salvage rates, the same does not apply for BMS. According to the data
obtained from infrapopliteal trials, DES bail-out stenting provides superior outcomes,
while primary bare metal stenting is no longer scientically justied [10,11].
Although this case was not technically challenging compared with other cases
presenting with long occlusions, bifurcation lesions, or distal pedal disease, it was
described because it summarizes the essence of percutaneous treatment and also
includes some technical key points crucial for the achievement of long-term clinical
success. First, the patient was suffering from limb-threatening ischaemia (rest pain
and possibly irreversible gangrene of the toe) caused by long multilevel stenotic femoropopliteal and infrapopliteal disease with poor distal run-off (Figure 8.1). Modern
treatment protocols consider the endovascular approach as the treatment of choice
in these cases [1]. Moreover, the patient was not t for surgery and consequently
percutaneous treatment was the only valid revascularization option. The rst step to
accomplishing technical and clinical success in infrapopliteal endovascular revascularization is excellent radiological assessment of the BTK vasculature and the choice
of the target vessel(s). Following balloon angioplasty of the SFA, a selective angiogram
with the catheter at the level of the tibial trifurcation was performed under magnication and at two different angles separated by 45°. This is essential for the correct
evaluation of infrapopliteal disease, as non-selective angiograms performed through
the sheath, especially prior to inow correction, do not provide adequate visualization of the atherosclerotic BTK lesions and the distal run-off status, while a single
projection might miss even an obvious lesion. Note that the obvious near-occlusion of
the proximal peroneal segment (Figure 8.1b), is not visible in the DSA run performed
in different angle (Figure 8.1c). This is why infrapopliteal endovascular procedures
should be performed using dedicated DSA C-arm units adequately equipped with a
large matrix in order to provide high-quality imaging and sufcient magnication.
The total extent of these peroneal atherosclerotic lesions (Figures 8.1 and 8.2) would
probably have been underestimated or even missed without selective magnied runs
at two different angles or if a conventional C-arm had been used.
The second key point was the decision to perform direct stenting using sirolimuseluting stents in a long lesion (9cm). This decision was based on the exceptional
reported outcomes of bail-out drug-eluting stenting in short lesions and the initial positive results obtained by direct stenting of long lesions in our department
[8,11–14]. DES placement was also decided because of the proximal location of the
lesion, as distal infrapopliteal stenting has been reported to perform poorly because
of the increased risk of fractures and/or deformation associated with reduced patency [15]. The long-term clinical and angiographic outcomes achieved in this case, as
well as the results of recent multicentre RCTs, validated this treatment choice.
Evidence base ACHILLES trial [10]
●
Seventeen European centres, randomized trial (1:1). Sponsors: Cordis, Johnson & Johnson.
●
Percutaneous transluminal angioplasty (PTA) (101 patients, 113 lesions) versus sirolimus-eluting
stents (SESs) (Cypher Select Plus©) (99 patients, 113 lesions).
●
Mean total lesion length was 26.9 mm. Lesions of length up to 90mm were treated.
●
At one year follow-up:
●
in-segment binary restenosis (by quantitative angiography), 22.4% for SES vs 41.9% for PTA (p = 0.019)
●
vessel patency, 75% for SES vs 57.1% for PTA (p = 0.025)
●
post hoc analysis of the composite endpoint including freedom from death, target lesion
revascularization, bypass/amputation and Rutherford Class ≥4 significantly favoured the SES
group over PTA treatment (p = 0.0284)
●
a trend towards improved wound healing was detected in the DES arm (61.7% vs 41.3%; p = 0.0628).
75Case 8 Below knee angioplasty: bare vs drug-eluting stents
Evidence base Destiny Study [16]
●
Seven European centres randomizing 140 CLI patients. Sponsor: Abbott.
●
Compared 66 patients treated with bare metal stents (Multi link Vision) with 74 patients treated with
everolimus-eluting stents (Xience V©).
●
Maximum lesion length, 40mm.
●
At one-year follow-up:
●
freedom from target lesion revascularization, 91% for Xience V vs 66% for BMS (p = 0.001)
●
primary patency, 85.2% for Xience V vs 54.4% for BMS (p = 0.0001
●
similar limb salvage rates in both arms.
Evidence base YUKON-BTX trial [17]
●
Multicentre randomized trial. Sponsor: Translumina GmbH.
●
Polymer-free sirolimus-eluting Yukon-BTX stent vs uncoated balloon expandable Yukon stent.
●
161 patients with CLI or intermittent claudication.
●
Maximum lesion length, 45mm.
●
At one-year follow-up:
●
superior clinical improvement of the patients enrolled in the DES Yukon BTX arm (Rutherford
class ≤2, 78.8% in the DES arm vs 63.9% in the BMS arm; p = 0.04)
●
Primary patency 80.6% for DES vs 55.6% for BMS (p = 0.004).
76 Interventional radiology and endovascular procedures
One could argue that limb salvage rates following infrapopliteal plain balloon
angioplasty remain similar to those achieved with DES. Nonetheless, inhibition of
re-stenosis by DES results in not only superior vessel patency, but also sustained
clinical improvement as demonstrated by the recent RCTs, which indicate that the
patient’s quality of life can be radically improved by preventing recurrent ischaemia,
leading to numerous re-interventions, or improving healing of ischaemic ulcers [18].
In this case a specially designed questionnaire was used to evaluate our patient’s
pre- and post-procedural quality of life. On a 0–10 scale the patient rated his preprocedural health status as 4/10, while aftera a one-year follow-up his health status
improved by four points (8/10). He also stated that he no longer experienced pain or
lifestyle-limiting claudication after three years follow-up.
A final word from the expert
Over the last decade, several investigators have reported the infrapopliteal application
of DES, usually for critical limb ischaemia treatment. Recent RCTs such as the ACHILLES
trial (sirolimus-eluting stents versus standard balloon angioplasty of the infrapopliteal
arteries) and the DESTINY trial (everolimus-eluting stents versus bare metal stents in the
infrapopliteal arteries) have reported significantly improved patency of the target lesions at
one-year follow-up. Additionally, in the ACHILLES trial a significantly improved composite
endpoint of event-free survival and a trend towards improved wound healing were detected
following DES application compared with balloon angioplasty. However, these results refer
to relatively short lesions, with the exception of results obtained recently by Katsanos et
al. [10] who reported encouraging long-term outcomes after full DES coverage of long
infrapopliteal lesions of up to 28cm (average, 7.7cm). It should be noted that cost issues arise
with the use of multiple DES in long lesions even though a relatively low number needed to
treat (NTT) and incremental cost-effectiveness ratios (ICERs) following infrapopliteal DES use
have been reported [19]. Other issues with infrapopliteal stenting include strict clinical and
imaging follow-up protocols to avoid occlusions where re-canalization is more demanding,
and care should be taken that DES placement does not impede any future bypass surgery
option where healthy unstented arterial segments are needed.
Current data conclusively demonstrate that the infrapopliteal use of DES significantly
reduces restenosis and clinically driven revascularization procedures compared with balloon
angioplasty and bare metal stenting, justifying their primary BTK application. Moreover, DES
utilized as a bail-out following suboptimal angioplasty result in superior long-term primary
patency rates compared to bail-out BMS. Balloon-expandable DES should not be used for
distal foot anatomical areas. In such cases, alternatives such as the emerging drug-coated
balloon technology should be considered.
References
1. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management
of Peripheral Arterial Disease (TASC II). Eur J Vasc Endovasc Surg 2007; 33 (Suppl 1):
S1–75.
2. Rooke TW, Hirsch AT, Misra S, et al. 2011 ACCF/AHA focused update of the guideline for
the management of patients with peripheral artery disease (updating the 2005 guideline).
Vasc Me d 2011; 16(6): 452–76.
3. Haider CR, Riederer SJ, Borisch, et al. High temporal and spatial resolution 3D timeresolved contrast-enhanced magnetic resonance angiography of the hands and feet.
J Magn Reson Imaging; 2011; 34(1): 2–12.
4. Karnabatidis D, Spiliopoulos S, Katsanos K, Siablis D. Below the knee drug-eluting stents
and drug-coated balloons. Expert Rev Med Devices 2012; 9(1): 85–94.
5. Spiliopoulos S, Katsanos K, Diamantopoulos A, et al. Does ultrasound-guided lidocaine
injection improve local anaesthesia before femoral artery catheterization? Clin Radiol
2011; 66(5): 449–55.
6. Novo S, Coppola G, Milio G. Critical limb ischemia: denition and natural history. Curr
Drug Targets Cardiovasc Haematol Disord 2004; 4(3): 219–25.
7. Romiti M, Albers M, Brochado-Neto FC, et al. Meta-analysis of infrapopliteal angioplasty
for chronic critical limb ischemia. J Vasc Surg 2008; 47(5): 975–81.
8. Siablis D, Karnabatidis D, Katsanos K, et.al Infrapopliteal application of sirolimus-eluting
versus bare metal stents for critical limb ischemia: analysis of long-term angiographic
and clinical outcome. J Vasc Interv Radiol 2009; 2 0(9): 1141–50.
9. Ong AT, Serruys PW. Technology insight: an overview of research in drug-eluting stents.
Nat Clin Pract Cardiovasc Med 2005; 2(12): 647–58.
10. Katsanos K, Spiliopoulos S, Krokidis M, et al. Does below-the-knee placement of dr ugeluting stents improve clinical outcomes? J Cardiovasc Surg (Torino) 2012; 53(2): 195–203.
11. Karnabatidis D, Spiliopoulos S, Diamantopoulos A, et al. Primary everolimus-eluting
stenting versus balloon angioplasty with bailout bare metal stenting of long infrapopliteal lesions for treatment of critical limb ischemia. J Endovasc Ther 2011; 18(1): 1–12.
12. Bosiers M, Deloose K, Verbist J, Peeters P. Percutaneous transluminal angioplasty for
treatment of ‘below-the-knee’ critical limb ischemia: early outcomes following the use of
sirolimus-eluting stents. J Cardiovasc Surg (Torino) 2006; 47: 171–6.
13. Commeau P, Barragan P, Roquebert PO. Sirolimus for below the knee lesions: mid-term
results of SiroBTK study. Cathet Cardiovasc Interv 2006; 6 8:793–8.
14. Scheinert D, Ulrich M, Scheinert S, et al. Comparison of sirolimus-eluting vs bare-metal
stents for the treatment of infrapopliteal obstructions. Eurointervention 2006; 2:169–174.
15. Karnabatidis D, Katsanos K, Spiliopoulos S, et al. Incidence, anatomical location, and
clinical signicance of compressions and fractures in infrapopliteal balloon-expandable
metal stents. J Endovasc Ther 200 9; 16(1): 15–22.
16. Bosiers M, Scheinert D, Peeters P, et al. Randomized comparison of everolimus-eluting
versus bare-metal stents in patients with critical limb ischemia and infrapopliteal arterial
occlusive disease. J Vasc Surg 2012; 55(2): 390–8.
17. Rastan A, Tepe G, Krankenberg H, et al. Sirolimus-eluting stents vs. bare-metal stents for
treatment of focal lesions in infrapopliteal arteries: a double-blind, multi-centre, randomized clinical trial. Eur Heart J 2011; 32(18): 2274– 81.
18. Karnabatidis D, Katsanos K, Siablis D. Infrapopliteal stents: overview and unresolved
issues. J Endovasc Ther 2009; 16 (Suppl 1): I153–62.
19. Katsanos K, Karnabatidis D, Diamantopoulos A, et al. Cost-effectiveness analysis of infrapopliteal drug-eluting stents. Cardiovasc Intervent Radiol 2013; 36(1): 90–7.
77Case 8 Below knee angioplasty: bare vs drug-eluting stents
CASE
9
Thrombolysis for acute lower limb
ischaemia
Athanasios Diamantopoulos
Expert commentary Panos Gkoutzios
Case history
A 57-year-old female was admitted to the A&E department suffering from symptoms
of acute ischaemia of the left lower limb. More specically, the patient complained
that her left leg felt cold and numb, with moderate motor and sensory loss evident.
Learning point
Acute limb ischaemia (ALI) is defined as a sudden event of perfusion deterioration, occurring less than
14 days from presentation, which may potentially cause limb loss [1,2]. It may be either the result of
rapid deterioration in a previously symptomatic patient suffering from peripheral arterial disease (PAD),
or an acute event in an asymptomatic patient [2]. Native arterial thrombosis remains the main cause of
the disease, accounting for 85% of cases, followed by embolism; less common causes include trauma
and acute arterial dissection [3]. Unfortunately, even today ALI is related to high major amputation and
mortality rates, mainly because of the presence of multiple comorbidities such as cardiopathy [2,3].
The patient’s previous medical history included a right common iliac artery (CIA)
to right common femoral artery (CFA) bypass followed by a right CFA to left CFA and
a left CFA to left popliteal artery bypass using a synthetic graft a year before admission. Post graft placement she underwent two endovascular procedures in order to
deal with distal anastomosis stenotic lesions. The remaining medical history included recurrent episodes of urinary tract infection (UTI), chronic obstructive pulmonary
disease (COPD), myocardial infraction (MI) with previous stenting, hypertension,
and hepatitis C. The baseline routine blood test results and observations are shown
in Table 9.1. Her medications included warfarin, isosorbide dinitrate (20mg twice
daily), ranitidine (300mg twice daily), atorvastatin (80mg once daily), bisoprolol
fumarate (5mg once daily), nicorandil (10mg twice daily), ramipril (5mg once daily),
isosorbide mononitrate (60mg once daily), naproxen (500mg twice daily), aspirin
(75mg once daily), calcium 600mg, colecalciferol 400 units chewable tablets (once
daily), and mirtazapine (30mg once daily).
Table 9.1 Baseline routine blood test results and observations
Hb 10.6g/dl Potassium 4.7mmol/L
White blood count
Platelets
INR 3.1 ratio Albumin level 44g/L
Class fibrinogen 3.35g/L Blood pressure 138/82mmHg
aPTT 1.4 ratio O
Sodium 142mmol/L Temperature 36.7°C
6.9 × 10
397 × 10
9
9
Creatinine
C-reactive protein <5mg/L
2
52μmol/L
99% on air
80 Interventional radiology and endovascular procedures
Both the vascular surgery team and the interventional radiology team were
contacted. In order to decide on the therapeutic plan, baseline imaging with a
CTA was ordered. The patient was transferred to the CT department for a contrast-enhanced CT scan which showed that both the right-to-left femoral–femoral
and the femoral–popliteal bypass grafts were thrombosed (Figures 9.1a, b) with
ow reconstitution at the popliteal artery just above the knee joint (Figure 9.1c).
A high-grade calcied stenosis of the proximal anterior tibial artery was also
evident.
Based on the CTA ndings as well as patient’s general health condition and previous medical history the consensus was to proceed with catheter-directed thrombolysis by direct puncture of the fem–fem graft. Other treatment options included
surgery and intravenous systemic thrombolysis.
(a) (b)
(c)(d)
Figure 9.1 (a) The right-to-left femoral–femoral crossover graft was thrombosed. In addition, (b) the
left side femoropopliteal bypass graft was thrombosed and (c, d) there was filling of the above knee
popliteal artery.
Learning point Treatment options for acute limb ischaemia
Treatment options for ALI include surgery, percutaneous endovascular treatments, and intravenous
systemic thrombolysis. More specifically, endovascular options include catheter-directed infusion
of pharmacological thrombolysis, mechanical thrombectomy, pharmacomechanical thrombolysis,
thrombus aspiration, or a combination of the above [4–8]. Nowadays, thrombolytic catheter-directed
treatment of ALI is an established and effective option [9–11].
Pharmacological thrombolysis is defined as thrombus dissolution by selective catheter directed
infusion of a thrombolytic agent. The indication for the procedure is the break up of thrombotic
occlusions of either native arteries or bypass grafts causing ALI in order to prevent limb loss. Published
data suggest significantly better results for thrombolysis than for surgery with respect to limb salvage
and mortality rates when the onset of ALI symptoms was less than 14 days previously as well as for
recent bypass graft occlusions [12,13].
Learning point Contraindications to percutaneous catheter-directed thrombolysis
Absolute contraindications to percutaneous catheter-directed thrombolysis include cases presented
with active or recent (within the past 10 days) internal or gastrointestinal bleeding that is not possible
to treat, known intracranial tumour, neurosurgery or intracranial trauma within the past three months, a
history of recent intracranial haemorrhage, abdominal surgery within the last three weeks, presence or
development of compartment syndrome or limb ischaemia associated with tissue loss that may require
urgent operation and/or irreversible nerve damage, and finally a known history of a cerebrovascular
event within the previous six months including transient ischaemic attacks within the past two months.
Relative contraindications include major non-vascular surgery or trauma during the past 10 days, a
history of gastrointestinal bleeding, uncontrolled hypertension, puncture of non-compressible vessel,
cardiopulmonary resuscitation within the last 10 days, recent eye operation, a history of severe contrast
allergy, hepatic failure, especially in cases with coagulopathy, bacterial endocarditis, pregnancy or postpartum stage, diabetic haemorrhagic retinopathy, and life expectancy less than one year [5,7,14].
The patient was informed about both the benets and the potential risks associated with the procedure and signed a written informed consent form. Under local
anaesthesia the right-to-left femoral–femoral graft was single-wall punctured using
ultrasound guidance and a 4Fr sheath was antegrade placed. A straight 4Fr catheter
with multiple side-holes was carefully advanced just distal to the sheath tip. Both
sheath and catheter were secured in place and thrombolysis through the catheter
was initiated as per institutional protocol. More specically, immediately after
establishment of safe access 5000IU of heparin was administered followed by 5mg
of recombinant tissue plasminogen activator (r-tPA) according to local protocol. A
pump infusion of r-tPA at a rate of 1mg/hour for the rst six hours followed by
0.5mg/hour for another 18 hours was then initiated. Additionally, infusion of 200IU/
hour of heparin was administered through the sheath’s side port pump in order
to prevent the development of new thrombus around the sheath and the catheter.
The patient was then transferred to a high dependency unit where she was closely
monitored for 24 hours (blood pressure measurement, heart rate, groin assessment).
81Case 9 Thrombolysis for acute lower limb ischaemia
Expert comment
Thrombolytic or fibrinolytic agents are extensively used for the treatment of ischaemia by enhancing
the endogenous thrombolytic system. Several thrombolytic agents are available, including urokinase,
natural streptokinase, anistreplase, tissue plasminogen activator (tPA), and recombinant tissue
plasminogen activators (r-tPAs) such as alteplase, reteplase, and tenecteplase. The most widely used
agents, depending on local protocols, experience, and availability, are urokinase and tPA or r-tPA.
Although there are is no available evidence showing the superiority of tPA over urokinase with respect
to safety and effectiveness, tPA is preferred because the initial lysis may be more rapid than that of
urokinase. Streptokinase is no longer the preferred agent as it has been demonstrated to be less
effective and more antigenic [15].
After initiation of the thrombolytic therapy patient must be kept under continuous surveillance in order
to detect any adverse events. Vital signs should be closely monitored and laboratory tests, including
HCT, Hb, INR, PT, PTT, and serum Cr, should be performed regularly.
Twenty-four hours after initiation of thrombolysis infusion the patient was
transfered back to the angiographic suite for a control angiogram. Digital subtraction angiography performed through the sheath demonstrated satisfactory ow
of the right-to-left femoral–femoral graft and the left side femoral–popliteal graft
with no signicant underlying lesions. There was a minor amount of residual
82 Interventional radiology and endovascular procedures
thrombus in the proximal segment of the peroneal artery, but the vessel re-formed
immediately distally and was patent to the ankle (Figures 9.2 and 9.3). The anterior
tibial artery was patent to the foot. The patient regained full motion and sensory
feeling in the previously ischaemic limb and the distal foot was signicantly warmer
than before the procedure. The consensus at that time was to terminate the thrombolysis and start immediate treatment with a therapeutic dose of low-molecular
(a)
(b) (c)
(a) (b)
Figure 9.2 Follow-up DSA showing satisfactory
flow in (a) the right-to-left femoral–femoral graft
and (b, c) the left side femoral–popliteal graft with
no significant underlying lesions being present.
Figure 9.3 DSA of the outflow vessels showed
(a) a small amount of residual thrombus in the
proximal segment of the peroneal artery, but the
vessel re-formed immediately distally and was
patent to the ankle. (a, b) The anterior tibial artery
was patent to the foot.
83Case 9 Thrombolysis for acute lower limb ischaemia
heparin combined with treatment with antiplatelet drugs (clopidogrel 75mg/day). The
long term anticoagulation plan was to restart the warfarin that the patient was receiving because of chronic atrial brillation. A 6Fr closure device was used to seal the
puncture site. No immediate complications were noted and the patient was discharged
the following day with instructions to visit the graft surveillance clinic after one month.
Evidence base
The STILE, ROCHESTER, and TOPAS trials are the most important randomized controlled trials
comparing catheter-directed thrombolysis with open surgery. These three trials all showed
comparable results for limb salvage between surgery and catheter-directed thrombolysis. However,
the mortality rates were lower for those cases treated with thrombolysis than for those treated
surgically: 16% vs 42% in the ROCHESTER trial [17], 6.5% vs 8.5% in the STILE trial [12], and 13.3% vs
15.7% in the TOPAS trial [18].
A significant conclusion of the STILE trial was that those patients with symptoms for less than 14 days
who were treated with catheter-directed thrombolysis had significantly lower amputation rates than
those who underwent surgical repair at six months (30% vs 11%) [3,12,18]. Both the TOPAS and the
STILE trials showed better outcomes after catheter-directed thrombolysis when ALI occurred in bypass
grafts rather in native arteries [12,18].
Learning point Risks of thrombolysis
Mortality, as a result of stroke, major bleeding, and myocardial infarction, is undoubtedly the major
risk for ALI patients treated with catheter-directed thrombolysis. More specifically, the incidence of
peripheral bleeding ranges from 1% to 25%, and the incidence of intracranial bleeding is between 0%
and 2.5% [3]. Less common complications include distal vessel embolization, compartment syndrome,
reperfusion syndrome, amputation, puncture site complications (pseudo-aneurysm), and contrastrelated complications (renal failure and allergy reactions). Finally, it must be remembered that rarely
some thrombolytic agents such as streptokinase may be associated with major allergic reactions.
Expert comment
One of the main advantages of
transcatheter thrombolysis is that
any underlying lesion can be
relatively safely treated. Treatment
of such lesions is mandatory
considering the superior vessel
patency rates at two years when
underlying lesions were identified
and treated compared with those
when this was not the case (79% vs
9.8%) [16]. The treatment of choice
in such cases should be primary
stenting, if this is possible.
Expert comment
There is enough evidence from
RCTs to support the use of
catheter-directed thrombolysis
in patients presenting with ALI
symptoms, especially when
for thrombosed bypass grafts.
Thrombolysis should be the firstline treatment option, especially
as there is published evidence
that whenever thrombolysis
fails, thrombectomy and/or graft
revision are associated with low
success rates [16].
Discussion
Since Dotter rst introduced catheter-directed thrombolysis, it has become established as an effective treatment option for patients suffering from ALI [9–11]. In
view of both the potential benets and the associated risks of such procedures, only
patients with salvageable limbs (i.e. the presence of a venous doppler signal and
incomplete motor and sensory loss) should be considered for this treatment [3].
Currently, a number of agents are used, and several administration techniques
have been proposed including regional intra-arterial infusion, intra-thrombus infusion, intra-thrombus bolusing, stepwise infusion, continuous infusion, graded infusion, and forced periodic infusion (pulse-spray technique). Regional intra-arterial
infusion may be performed with the catheter placed just proximal to the occlusion or with its tip embedded in its most proximal segment. The intra-thrombus
technique is characterized by delivery of the lytic agent inside the occlusion. Intrathrombus bolusing refers to initial administration of concentrated brolytic agent
in the thrombus. Stepwise infusion involves the initial delivery of the agent in the
proximal segment of the thrombus followed by stepwise advancement of the catheter to the distal segment. Continuous infusion is the constant delivery of the agent
using a pump. Graded infusion is characterized by time-related delivery of the drug.
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