Catheter-directed thrombolysis for acute limb ischemia

148 Pages·2016·1.11 MB·English

Catheter-direCted thrombolysis for
aCute limb isChemia
A.M. Schrijver
Catheter-directed thrombolysis for acute limb ischemia
thesis, utrecht university, the Netherlands
Copyright © by a.m. schrijver 2016
isbN: 978-94-6169-818-6
layout: optima Grafische Communicatie, rotterdam, the Netherlands
Printed by: optima Grafische Communicatie, rotterdam, the Netherlands
the printing of this thesis was financially supported by angiocare, Chipsoft, W. l. Gore & associ-
ates, Krijnen medical innovations, lamepro, takeda Nederland, and st. antonius Ziekenhuis.
financial support by the dutch heart foundation for the publication of this thesis is
gratefully acknowledged.
Catheter-direCted thrombolysis for aCute limb isChemia
Catheter-geleide trombolyse voor acute ischemie van de extremiteit
(met een samenvatting in het Nederlands)
Proefschrift
ter verkrijging van de graad van doctor aan de universiteit utrecht op gezag van de rector
magnificus, prof.dr. G.J. van der Zwaan, ingevolge het besluit van het college voor promoties in
het openbaar te verdedigen op donderdag 24 maart 2016 des middags te 4.15 uur
door
Anne Marjolein Schrijver
geboren op 6 augustus 1983 te leiden
Promotor: Prof.dr. f.l. moll
Copromotor: dr. J.P.P.m. de Vries
CoNteNts
Chapter 1 General introduction and thesis outline 7
Chapter 2 Pharmacomechanical thrombolysis for acute arterial limb occlusions 15
In preparation
Chapter 3 long-term outcomes of catheter-directed thrombolysis for acute lower 25
extremity occlusions of native arteries and prosthetic bypass grafts
Ann Vasc Surg 2015, Epub ahead of print
Chapter 4 Catheter-directed thrombolysis for acute upper extremity ischemia 39
J Cardiovasc Surg (Torino) 2015;56(3):433-9
Chapter 5 advancements in catheter-directed ultrasound-accelerated thrombolysis 53
J Endovasc Ther 2011;18(3):418-34
Chapter 6 initial results of ultrasound-accelerated thrombolysis in arterial 77
thromboembolic obstructions of the lower extremities; a feasibility study
Cardiovasc Interv Radiol 2012;35(2):279-85
Chapter 7 dutch randomized trial comparing standard catheter-directed 91
thrombolysis versus ultrasound-accelerated thrombolysis for
thromboembolic infrainguinal disease: design and rationale
[isrCtN72676102]
Trials 2011;12(1):20
Chapter 8 dutch randomized trial comparing standard catheter-directed 105
thrombolysis and ultrasound-accelerated thrombolysis for arterial
thromboembolic infrainguinal disease - duet
J Endovasc Ther 2015;22(1):87-95
Chapter 9 summary and general discussion 121
Chapter 10 Nederlandse samenvatting 131
Chapter 11 review Committee 137
dankwoord 141
author’s publication list 145
author’s curriculum vitae 147

Chapter 1
General introduction and thesis outline

General introduction and thesis outline 9
aCute limb isChemia
acute limb ischemia is a vascular emergency. the incidence of acute limb ischemia is estimated
to be 14 per 100,000 in the general population and to form 10% to 16% of the vascular workload.1
When not treated promptly and adequately it is associated with significant limb loss and death.
many patients suffering from acute limb ischemia have extensive cardiovascular disease, which
makes them high-risk patients. the major cause of acute limb ischemia is thrombosis of underly-
ing atherosclerotic disease. atherosclerotic plaque rupture causes platelet activation, leading to
platelet adherence and altered flow, which results in thrombosis. the second most common
cause of acute limb ischemia is embolism, usually of cardiac origin. more rare underlying causes
are cystic adventitial disease, popliteal entrapment syndrome, popliteal aneurysm, vasculitis,
hyperhomocysteinemia and paraneoplastic syndrome.2
initial clinical examination is crucial in patients with acute limb ischemia. the classical signs
and symptoms of patients with acute limb ischemia are categorized by the “six Ps” (pain, pallor,
paralysis, pulse deficit, paresthesia, and poikilothermia). in 1986 a clinical classification for acute
limb ischemia was published, that was later known as the rutherford classification (table).3
if sensation and motor function are present, viability of the limb is not immediately threatened
and the patient can be treated semi-elective. in case of loss of sensation or muscle weakness,
prompt surgical intervention is required, since ultimate limb loss is likely.
Table. rutherford classification for acute limb ischemia
Class Clinical signs
i Viable–not immediately threatened, no sensory loss or muscle weakness, arterial doppler signal is audible.
iia marginally threatened–salvageable if promptly treated, minimal sensory loss, no muscle weakness, arterial
doppler signal is often inaudible.
iib immediately threatened–salvageable with immediate revascularization, sensory loss associated with rest pain
in more than the toes, mild to moderate muscle weakness, arterial doppler signal is usually inaudible.
iii irreversible–major tissue loss or permanent nerve damage inevitable if there is significant delay before
intervention, profound limb anesthesia and paralysis, arterial and venous doppler signal is inaudible.
surGiCal thromboemboleCtomy
over a long period of time, surgical thromboembolectomy has been the standard of care for
patients with acute limb ischemia. in 1963 the introduction of the fogarty catheter (a flexible
tube, with a balloon attached to its tip through which thrombus is extracted) allowed large
amounts of thromboembolic material to be removed rapidly to restore blood flow to ischemic
tissues.4 disadvantages of this technique are damaging the endothelium and often leaving the
underlying cause of the thrombus, an atherosclerotic plaque, untreated. furthermore, it can be
challenging to treat small arteries in the foot or forearm with a thromboembolectomy catheter.
in addition, up to 30% of thromboembolectomies may show residual thrombus on angiogram.5
10 Chapter 1
Catheter-direCted thrombolysis
Catheter-directed thrombolysis was introduced in the 1980s and its use has widely increased
ever since. the benefits of catheter-directed thrombolysis compared with surgery are gentler and
more complete clot removal, which allows the preservation of endothelium, its less invasiveness,
and the possibility to visualize and, if necessary, to treat an underlying atherosclerotic lesion
or anastomotic stenosis by endovascular means. the main limitations include failure to achieve
complete lysis, prolonged time to revascularization and the occurrence of hemorrhagic compli-
cations. so far, there have been three large randomized controlled trials comparing surgery to
catheter-directed thrombolysis.
in the rochester trial a total of 114 patients with limb-threatening ischemia of less than 7 days’
duration were randomized to thrombolytic therapy or surgical therapy. thrombolytic therapy
resulted in complete lysis of the thrombus in 70%. although limb salvage rate at 12 months did
not differ between the groups, cumulative survival rate at 12 months was significantly higher in
the thrombolysis group.6
in the stile trial a total of 393 patients with native arterial or bypass graft occlusions were
randomized to either optimal surgical treatment or catheter-directed thrombolysis with recom-
binant tissue plasminogen activator or urokinase. Patients with progressive limb ischemia in the
previous 6 months were eligible for inclusion in the study. there was no significant difference in
death or major amputation between the groups, but patients that underwent surgical treatment
had significantly less ongoing/recurrent ischemia as compared to thrombolysis. a subgroup
analysis stratified by duration of ischemia (acute (0-14 days of worsening ischemia) versus
chronic (>14 days) ischemia) showed that among patients with acute ischemia, surgery was as-
sociated with more major amputations compared with thrombolysis. the authors concluded that
combining a treatment strategy of catheter-directed thrombolysis for acute limb ischemia with
surgical revascularization for chronic limb ischemia offers the best overall results. it is noteworthy
that the study terminated prematurely because of significant failure of placement of the catheter
in the thrombolysis group.7
in the toPas trial a total of 454 patients with acute (<14 days) arterial occlusions of the lower
limbs, were randomized to surgical treatment (surgical thromboembolectomy or bypass graft-
ing) or catheter-directed thrombolysis. the amputation-free survival rates at 6 months and 1 year
did not significantly differ between the groups. however, during the first 6 months after initial
treatment, patients who were assigned to surgery underwent nearly twice as much open surgical
procedures, as compared to the patients that were assigned to thrombolysis. a 12.5 percent
incidence of major hemorrhage with urokinase was found. despite its association with a higher
incidence of hemorrhagic complications, intra-arterial infusion of urokinase reduced the need for
surgical procedures, with no significant increase in amputation or death.8