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EDUCATIONAL OBJECTIVE: Readers will be able to diagnose, classify, differentiate, and offer treatment op- POINTS FROM
CME
CREDIT tions for acute and critical limb ischemia LECTURES BY
MEHDI H. SHISHEHBOR, DO, PhD, MPH CLEVELAND
Director, Endovascular Services, and Staff,
Interventional Cardiology and Vascular Medicine, Heart CLINIC
and Vascular Institute, Cleveland Clinic
AND VISITING
FACULTY
TABLE 2
Clinical classification of acute limb ischemia
Findings Doppler signals
Sensory Muscle
Category Prognosis loss weakness Artery Vein
II Threatened
IIb Immediately Salvageable with immediate More than Mild, moderate Usually Audible
revascularization toes inaudible
• Poikilothermia (inability to regulate tem- However, if the arterial pulse is present, the
perature). venous pulse should be next to it. Knowing
A good pulse examination includes mea- the other criteria can determine the catego- Peripheral
suring the ankle-brachial index and a Dop- ry, so not being certain of the venous pulse artery disease
pler examination of both legs. A neurologic should not deter a clinician from assessing the
examination focusing on sensory and motor other factors.
itself does not
function is critical for determining the level of Category I is “viable.” Patients have in- cause ulcers:
ischemia and the urgency of intervention. tact sensory and motor functions and audible instigating
pulses. Patients in this category should be ad-
Classification of acute limb ischemia mitted and possibly started on anticoagulation factors should
If it is determined that a patient has acute leg therapy and referred to a vascular specialist be sought
ischemia, it is important to categorize the con- within hours.
dition using the classification system devised Category IIa is “threatened.” Sensation is
by the Society of Vascular Surgery and Inter- starting to be lost but motor function is still
national Society of Cardiovascular Surgery present. These patients are considered to have
(TABLE 2).9 The category establishes the type reversible ischemia, analogous to myocardial
and urgency of treatment. This classification infarction of the leg, and they require immedi-
system is simple and depends on factors that ate attention.
can be assessed easily by nonspecialists:
Category IIb is similar and it also requires
• Pulses—arterial and venous pulses assessed
immediate attention.
by Doppler ultrasonography
Category III is usually irreversible, with
• Sensation—the patient closes the eyes and
loss of motor function and sensation.
answers if he or she can feel the examiner’s
touch
• Motor function—can the patient move his ■■ CAUSES OF ACUTE LIMB ISCHEMIA
or her toes? Thrombosis accounts for about 50% of cas-
Venous pulses can be difficult to assess. es. Underlying causes of the thrombosis are
CL EV E L AND CL I NI C J O URNAL O F M E DI CI NE V O L UM E 81 • NUM BE R 4 AP RI L 2014 211
ACUTE AND CRITICAL LIMB ISCHEMIA
artherosclerosis (native or bypass), aneurysm, when the patient is standing (dependent ru-
trauma, vasculitis (eg, in a rheumatologic dis- bor), but pale when the foot is elevated (el-
ease such as lupus), and hypercoagulable states evation pallor).
(particularly in patients with cancer). Confirming that a patient has dependent
Embolism accounts for about 30% of cases. rubor can be challenging, especially in people
Emboli usually arise from plaque rupture in with dark skin. Classically, redness is seen
atherosclerotic arteries or a clot breaking off when the leg is down and disappears with el-
from an aneurysm or from within the heart evation, but in cellulitis, redness can also be
in patients with atrial fibrillation or another reduced by elevating the leg. A foot that is hot
underlying heart disease. Paradoxical embo- to the touch is an indication of infection and
lism, caused by an embolism crossing the heart not lack of perfusion alone.
through an opening such as a patent foramen The hemodynamic definition of critical
ovale, is rare. limb ischemia is11:
Uncommon causes include arterial dis- • Ankle-brachial pressure index less than
section following trauma, adventitial cystic 0.4
disease, popliteal artery entrapment, ergot- • Reduced toebrachial pressure index, ie,
ism (from consuming fungus-contaminated less than 0.7
grains), and human immunodeficiency virus • Reduced transcutaneous pressure of oxy-
arteriopathy. gen (Tcpo2), ie, less than 40 mm Hg.
The physical examination provides clues From 15% to 20% of patients with claudi-
to the origin: livedo reticularis (purple dis- cation will progress to critical ischemia over
coloration in a mottled pattern) and blue nail their lifetime, and in patients with claudica-
beds indicate that an embolus is likely. Tests, tion who also have diabetes, the risk is nearly
including electrocardiography, echocardiogra- 10 times higher. Without revascularization,
phy, and computed tomography of the chest the risk of amputation within 1 year is 73%
and abdomen to look for an aneurysm, can for patients in Rutherford class IV and 95%
help identify the cause. Ultrasonography of for patients in class V or VI.
Evidence of the popliteal arteries should also be consid-
Revascularization and limb preservation
pain at rest is ered to search for an aneurysm.
Preserving the limb is a prime goal. For pa-
the need to get ■■ CRITICAL LIMB ISCHEMIA
tients who have an amputation, the mortal-
up at night to ity rate is 40% within 2 years.8 These patients
Critical limb ischemia is more likely than tend to be elderly, and after an amputation,
dangle the leg acute limb ischemia to be seen in a general most will not learn to use a prosthesis and
over the bed practice. Many aspects need to be addressed resume their previous level of activity. Other
simultaneously, by different specialists: vas- treatment objectives are to relieve pain, re-
cular and endocrine systems, infection, and duce cardiovascular risk, and minimize proce-
wound care. The most successful management dural complications.
strategy is a dynamic approach using every Although limb preservation is not a con-
piece of information.10 troversial goal, best practices to preserve limbs
The Rutherford classification of periph- are not universally available. Goodney et al12
eral artery disease has six categories based on studied variation in the United States in the
the clinical presentation, with categories I use of lower-extremity vascular procedures
through III being mild to severe claudication. for critical limb ischemia. They defined “low-
We discuss here only the more severe catego- intensity” to “high-intensity” regions of the
ries: IV (pain at rest), V (tissue loss), and VI country depending on the proportion of pa-
(gangrene). tients who underwent a vascular procedure in
Strong indicators of pain at rest are that the year before amputation. They found con-
the patient has to get up at night to dangle the siderable variation, but even in the region of
leg over the bed or walk a few steps, or sleeps highest intensity, more than 40% of patients
in a chair, or refuses to elevate the leg because did not have a vascular procedure in the year
of pain. The affected leg tends to appear red before amputation.
212 CLEV ELA N D C LI N I C JOURNAL OF MEDICINE VOL UME 81 • N UM BE R 4 AP RI L 2014
SHISHEHBOR
Peroneal
artery
Posterior
tibial
artery
Calcaneal
branch
Anterior
tibial
artery Lateral
Medial plantar
plantar branch
branch
CCF
Medical Illustrator: Beth Halasz ©2014
FIGURE 1. The foot and ankle can be divided into six territories called angiosomes, based on the artery
supplying them. The concept can help in locating the obstruction in the specific artery in patients with
lower-extremity ischemic ulcers and in planning revascularization.
Similarly, Jones et al13 mapped amputation sociation Guidelines for the Management
rates by US state and found significant varia- of Patients With Peripheral Arterial Disease
tion even after adjusting for risk factors such (Lower Extremity, Renal, Mesenteric, and
as tobacco use and obesity. Abdominal Aortic) state that the tibial or
Controversy surrounds the specifics of re- pedal artery that is capable of providing con-
vascularization treatment, as in many fields tinuous and uncompromised outflow to the
in vascular medicine. However, most experts foot should be used as the site of distal anasto-
agree that improved perfusion is the goal. mosis.14 These guidelines do not yet mention
The Trans-Atlantic Inter-Society Consen- endovascular therapy.
sus for the Management of Peripheral Artery Angiosomes guide revascularization
Disease recommends revascularization as the In the past few years, the ability to facilitate
best treatment for patients with critical limb healing of foot ulcers has improved. An-
ischemia.8 In addition, the American Col- giosomes—regions of vascularization sup-
lege of Cardiology and American Heart As- plied by specific arteries—can be mapped
CL EV E L AND CL I NI C J O URNAL O F M E DI CI NE V O L UM E 81 • NUM BE R 4 AP RI L 2014 213
ACUTE AND CRITICAL LIMB ISCHEMIA
on the skin, similar to the way dermatomes patients have ulcers in the toes and distal foot.
are mapped for neural innervation (FIGURE 1). The toe-brachial index must be specifically or-
The foot and lower leg region has six angio- dered in most institutions (if the first toe has
somes perfused by three arteries that branch an ulcer, the second toe should be assessed).
off the popliteal artery after it passes behind The toe-brachial index is also important if
the knee: the ankle-brachial index cannot be obtained
• The anterior tibial artery supplies the dorsum because of calcified, noncompressible arteries
of the foot and the front of the lower limb. in the ankle. A normal toe-brachial index is
• The posterior tibial artery supplies the greater than 0.7.
plantar surface of the foot via three branch- The segmental blood pressure examina-
es—the medial plantar, lateral plantar, and tion compares blood pressure measurements at
calcaneal branches. multiple sites in the lower extremity. A drop
• The peroneal artery supplies the lateral of more than 20 mm Hg between segments in-
part of the foot with collaterals to the an- dicates obstruction at that location. The test
terior and posterior tibial arteries if they is simple and noninvasive and often can re-
are compromised. place computed tomography.20
Studies have compared angiosome-based
treatment vs revascularizing the best available Transcutaneous oximetry
artery (thus depending on collateral flow to Transcutaneous oximetry measures the Tcpo2
compensate to surrounding areas). They have from 1 to 2 mm deep in the skin from local
found that regardless of whether an endovas- capillaries. Measured adjacent to an ulcer, it is
cular or bypass method of revascularization useful to predict wound healing and to assess
was used, an angiosome-based approach led to the response to hyperbaric oxygen therapy.21
significantly higher amputation-free survival The values are:
rates.15–17 • Normal > 70 mm Hg
Patients typically do not have blockage • Impaired wound healing < 40 mm Hg
of only a single tibial artery. Graziani et al18 • Critical limb ischemia < 30 mm Hg.
An angiosome- assessed the vascular lesions in 417 patients Although most agree that a Tcpo2 below
40 mm Hg requires revascularization, low
based approach with critical limb ischemia and found that
multiple below-knee arteries were frequently values can arise from many causes other than
is better than involved. This makes it difficult to decide peripheral artery disease, including high alti-
targeting the where to target revascularization efforts, and tude, pulmonary disease, heart failure, edema,
the angiosome concept helps with that. inflammation, callus, and skin diseases such as
best available scleroderma.
artery ■■ ASSESSING WOUND PERFUSION
Ankle- and toe-brachial indices assess Skin perfusion pressure
perfusion better predicts healing
The ankle-brachial index19 is a good superfi- Skin perfusion pressure is a measure of the cap-
cial assessment of perfusion. Multiple epide- illary opening pressure after occlusion and is
miologic studies have shown the prognostic another way to assess perfusion. This test is not
value of the ankle brachial index beyond the routinely done and must be specially requested.
traditional risk factors and even the Framing- The test is performed by inflating a blood
ham risk score.19 Values: pressure cuff on the leg until blood flow is oc-
• Normal 1.1–1.30 (> 1.31 is abnormal and cluded, then using laser Doppler to determine
consistent with calcified vessels, and is an reactive hyperemia, ie, the gradual return of
unreliable measure) blood flow during controlled pressure release.
• Low normal 0.91–1.00 The pressure at which movement is detected
• Mild disease 0.71–0.90 is the skin perfusion pressure.22
• Moderate disease 0.41–0.70 The laser Doppler probe emits and detects
• Severe disease ≤ 0.40. light scattered in the tissue. Light hitting mov-
However, the ankle-brachial index as- ing blood cells undergoes a change in frequen-
sesses perfusion only to the ankle, and many cy, ie, a Doppler shift. An algorithm converts
214 CLEV ELA N D C LI N I C JOURNAL OF MEDICINE VOL UME 81 • N UM BE R 4 AP RI L 2014
SHISHEHBOR
the optical information in the skin perfusion can also consider cilostazol (Pletal); however,
pressure by capturing the onset of capillary flow the role of this agent in patients with critical
return and determining the pressure at which limb ischemia is less defined.
flow returns. Categories of results:
• > 50 mm Hg—normal ■■ BYPASS OR ANGIOPLASTY?
• 40–50 mm Hg—mild ischemia (wound heal- The Bypass Versus Angioplasty in Severe
ing probable) Ischaemia of the Leg (BASIL) trial24 ran-
• 30–40 mm Hg—moderate ischemia domly assigned 452 patients with severe
(wound healing uncertain) limb ischemia due to infrainguinal athero-
• < 30 mm Hg—critical limb ischemia (wound sclerosis to receive either surgery-first or
healing unlikely). angioplasty-first care and followed them for
Skin perfusion pressure testing has the advan- 5.5 years.
tages of not being affected by vessel calcifica- No significant differences between the
tion, thickened skin, or edema. It can be used two groups were found in amputation-free
on the plantar aspect of the foot and on digits. survival, deaths, or health-related quality
Recent small studies indicate that it is more of life. However, hospital costs associated
sensitive for predicting wound healing than with the surgery-first strategy were about
Tcpo2 measures. one-third higher. As expected, more pa-
On the other hand, skin perfusion pressure tients in the surgery group developed a
testing is not useful for predicting response to wound infection, and more patients in the
hyperbaric oxygen therapy. Also, blood flow angioplasty group required bypass surgery
occlusion by the cuff may be painful. at some point.
Intraoperative fluorescence angiography The conclusion that can be reached from
Intraoperative fluorescence angiography is this study is that patients presenting with
used to assess flap viability during reconstruc- severe limb ischemia due to infrainguinal
tive surgery and is being studied to determine atherosclerotic occlusive disease who are
its usefulness for assessing tissue viability in suitable for both surgical and interventional The classic
limb ischemia. procedures can be treated with either method.
The test provides real-time assessment of However, most experts consider endovascular assessment
capillary perfusion, determining surface tissue therapy as the first option in many patients. tool is the
viability. The imaging head contains a digi- The National Institutes of Health recently
tal camera, a laser light source, and a distance funded a study to compare contemporary en- ankle-brachial
sensor. The test requires intravenous admin- dovascular therapy vs surgery in patients with and toe-
istration of indocyanine green, which binds critical limb ischemia. brachial index
to plasma proteins and is cleared through
the liver, making it safe for patients with re- ■■ TAKE-HOME POINTS
nal dysfunction. It cannot be used in patients In the last decade, significant endovascu-
with allergies to iodine contrast, penicillin, or lar advances have been made. New devices
sulfa.23 and techniques have enhanced our ability
to treat high-risk patients who have criti-
■■ PREVENTION TARGETS cal limb ischemia. The combination of risk
CARDIOVASCULAR RISK FACTORS factor modification, accurate diagnosis, and
Preventive measures are the same as for car- aggressive revascularization should prevent
diovascular disease, ie, aggressive risk-factor limb loss in many of these patients. For the
modification: quitting smoking, lowering primary care physician, a low threshold for
low-density lipoprotein cholesterol, reducing assessing perfusion in patients with critical
blood pressure, controlling diabetes, and man- limb ischemia is important using a screening
aging heart failure. ankle-brachial index and toe-brachial index.
Dual antiplatelet therapy should be insti- These patients should promptly be referred
tuted with aspirin and clopidogrel (Plavix) in to a vascular specialist for further evaluation
patients undergoing revascularization. One and treatment. ■
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216 CLEV ELA N D C LI N I C JOURNAL OF MEDICINE VOL UME 81 • N UM BE R 4 AP RI L 2014