vascular pain and medical treatment of intermittent claudication chp 37, 40 maureen tedesco, md...
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Vascular PainVascular Painandand
Medical Treatment of Medical Treatment of Intermittent ClaudicationIntermittent Claudication
Chp 37, 40 Chp 37, 40 Maureen Tedesco, MDMaureen Tedesco, MD
Vascular SurgeryVascular Surgery
August 29, 2005August 29, 2005
PainPain
Nociceptive pain: associated with injurious Nociceptive pain: associated with injurious stimulationstimulation
Neuropathic pain: transmitted in absence Neuropathic pain: transmitted in absence of injury of injury
Location, duration, quality, severity, Location, duration, quality, severity, intensity intensity
Can result from physical stimuli, or Can result from physical stimuli, or chemical effects (pH change, mediators)chemical effects (pH change, mediators)
Nociceptive painNociceptive pain
Transmitted in small unmyelinated A delta Transmitted in small unmyelinated A delta and C nerve fibersand C nerve fibersLarge and medium arteries have 2 types Large and medium arteries have 2 types of innervation: afferent (sensory) and of innervation: afferent (sensory) and autonomic (sympathetic) nervesautonomic (sympathetic) nervesarteries: stimulated by trauma, stretch or arteries: stimulated by trauma, stretch or shear shear Veins: stimulated by stretch Veins: stimulated by stretch Relieved by resolution of stimuli Relieved by resolution of stimuli
Intermittent Claudication (IC) Intermittent Claudication (IC)
reduction of arterial perfusion to an extent that it reduction of arterial perfusion to an extent that it is inadequate to meet the needs of working is inadequate to meet the needs of working musclesmusclesCommon in Gastrocnemius-soleus muscle group Common in Gastrocnemius-soleus muscle group Never at rest, occurs post exertion of specific Never at rest, occurs post exertion of specific amount, disappears quickly after cessation amount, disappears quickly after cessation Burning, aching, crampingBurning, aching, crampingNo trophic lesions No trophic lesions Ischemic neuropathy (A delta and C fibers), Ischemic neuropathy (A delta and C fibers), lactic acidosis lactic acidosis
Psuedoclaudication: Neurogenic Psuedoclaudication: Neurogenic claudicationclaudication
lumbosacral neurospinal compression syndrome lumbosacral neurospinal compression syndrome (spinal stenosis) (spinal stenosis) more common b/l, more diffuse pain (buttocks to more common b/l, more diffuse pain (buttocks to feet), feet), associated with numbess/paresthesias; associated with numbess/paresthesias; relief with bending over while walking/ postural relief with bending over while walking/ postural changeschanges minimal or no change in Doppler ankle pressure minimal or no change in Doppler ankle pressure index during lower extremity pain while walking index during lower extremity pain while walking excludes arterial occlusive diseaseexcludes arterial occlusive disease
popliteal entrapment syndrome: exercise popliteal entrapment syndrome: exercise induced pain in anterolateral aspect of leg; induced pain in anterolateral aspect of leg; LE claudication in young pts LE claudication in young pts
chronic compartment syndrome: ischemia chronic compartment syndrome: ischemia d/t decreased AV pressure differential d/t decreased AV pressure differential from venous engorgement and from venous engorgement and compartment tissue hypertensioncompartment tissue hypertension
Aortic and other larger artery painAortic and other larger artery pain
Aortic aneurysmal rupture: sudden, Aortic aneurysmal rupture: sudden, steady, burning, penetrating steady, burning, penetrating
Aortic dissection: substernal or Aortic dissection: substernal or interscapular tearing, rippinginterscapular tearing, ripping
Extracranial Carotid A dissection: burning Extracranial Carotid A dissection: burning pain in lateral neckpain in lateral neck
Vasculitic pain Vasculitic pain
Diffuse, aching painDiffuse, aching pain
Diffuse pain over affected area (temple Diffuse pain over affected area (temple pain d/t temporal arteritis )pain d/t temporal arteritis )
Rest Pain, Ulcers, GangreneRest Pain, Ulcers, Gangrene
Signals impending limb lossSignals impending limb loss
Requires surgical intervention: arterial Requires surgical intervention: arterial reconstruction or amputationreconstruction or amputation
Mortality >50% over next 5 yrs Mortality >50% over next 5 yrs
Rest PainRest Pain
Diffuse, poorly localized aching/burning in Diffuse, poorly localized aching/burning in distal footdistal foot
Symptoms resolve if foot is hung over Symptoms resolve if foot is hung over edge of bed or pt risesedge of bed or pt rises
Arterial UlcerationArterial Ulceration
(non-diabetic pt) (non-diabetic pt) Shallow, nonhealing, Shallow, nonhealing, pallid erosion of skinpallid erosion of skin
Unremitting and Unremitting and severe pain severe pain
Tx: urgent Tx: urgent revascularization or revascularization or amputation amputation
GangreneGangrene
Tissue death Tissue death
Pain: ischemic Pain: ischemic neuropathy, skin and neuropathy, skin and subcutaneuous tissue subcutaneuous tissue necrosis, osteomyelitis, necrosis, osteomyelitis, and ascending and ascending infectioninfection
Paradoxically less pain Paradoxically less pain than expected as distal than expected as distal feet may be insensate feet may be insensate
Blue toe syndrome Blue toe syndrome
Atheroembolism to toes Atheroembolism to toes or distal foot occurs b/c of or distal foot occurs b/c of digital or branch artery digital or branch artery occlusion from occlusion from clot/atheroma that has clot/atheroma that has embolized into the distal embolized into the distal circulation from a circulation from a proximal sourceproximal source
Pain is uncommon until Pain is uncommon until digital ischemia is severe digital ischemia is severe
Diabetic footDiabetic foot
Chronic LE and foot Chronic LE and foot pain, nonhealing pain, nonhealing ulceration, toe ulceration, toe gangrenegangreneunderlying pathologyunderlying pathology- diabetic neuropathy - diabetic neuropathy - structural changes- structural changes
- inability to fight - inability to fight bacterial infections bacterial infections - not ischemia- not ischemia
Pain associated with Small artery Pain associated with Small artery DiseaseDisease
Raynaud’s Syndrome: Raynaud’s Syndrome: coolness, pallor, numbness, coolness, pallor, numbness, cyanosis, paincyanosis, pain- Abnormal arterial reactivity- Abnormal arterial reactivity- Dull acheness, fiery pain - Dull acheness, fiery pain Raynaud’s phenomenon: Raynaud’s phenomenon: digital arterial occlusion due digital arterial occlusion due to rheumatoid conditions; to rheumatoid conditions; digital vasoconstrictiondigital vasoconstriction vasodilation vasodilation
-Fingertip ulceration and -Fingertip ulceration and necrosis necrosis
Pain associated with Small artery Pain associated with Small artery DiseaseDisease
Buerger’s Disease (thrombangiitis Buerger’s Disease (thrombangiitis obliterans): nonatherosclerotic necrotizing obliterans): nonatherosclerotic necrotizing process involving arteries, veins and process involving arteries, veins and nerves in the extremities; nerves in the extremities;
severe, unremitting, aching, burning and severe, unremitting, aching, burning and agonizing foot and hand pain agonizing foot and hand pain
Pain associated with Venous Pain associated with Venous DisordersDisorders
DVT: painless LE edema, CPDVT: painless LE edema, CPVaricosities: diffuse aching pain or burning pain Varicosities: diffuse aching pain or burning pain secondary to stretch stimulation secondary to stretch stimulation Postphlebitis syndrome: chronic LE edema, Postphlebitis syndrome: chronic LE edema, secondary venous varicosities, skin changes secondary venous varicosities, skin changes (stasis pigmentation, eczema, subcutaneous (stasis pigmentation, eczema, subcutaneous atrophy, skin breakdown, chronic nonhealing atrophy, skin breakdown, chronic nonhealing ulcerations)ulcerations)Superficial phlebitis: chemical irritation of the Superficial phlebitis: chemical irritation of the intima of peripheral veins; IV’s, catheters; intima of peripheral veins; IV’s, catheters; palpable cord, pain well localized, burningpalpable cord, pain well localized, burning
Venous Stasis pigmentation Venous Stasis pigmentation
Pain associated with Lymphatic DxPain associated with Lymphatic Dx
Lymphedema praecox- idiopathic Lymphedema praecox- idiopathic nonvenous swelling of a lower extremity nonvenous swelling of a lower extremity
Lymphedema not painful unless cellulitis Lymphedema not painful unless cellulitis or lymphangitis is present or lymphangitis is present
Pain Associated with AmputationPain Associated with Amputation
Acute: related to surgery; resolves within Acute: related to surgery; resolves within weeksweeksStump hematoma, necrosis Stump hematoma, necrosis Limb sensation, phantom limb pain: Limb sensation, phantom limb pain: diminishes within months-years; may need diminishes within months-years; may need treatment treatment Late postamputation pain due to poor Late postamputation pain due to poor fitting prosthesis, neuroma, ischemia, fitting prosthesis, neuroma, ischemia, DVT, progressive autonomic dysfunction DVT, progressive autonomic dysfunction
Medical Treatment of Intermittent Medical Treatment of Intermittent Claudication Claudication
Platelet InhibitorsPlatelet Inhibitors
ASA, PlavixASA, Plavix
VasodilatorsVasodilators
Trental, Pletal, Praxilene, Levocarnitine, Trental, Pletal, Praxilene, Levocarnitine, Chelation Tx, Arginine, Chelation Tx, Arginine, Ginko bilobaGinko biloba, , Buflomedil, Ketanserin, Niacin, LovastatinBuflomedil, Ketanserin, Niacin, Lovastatin
Intermittent claudicationIntermittent claudication
Clinical condition of ischemic extremity Clinical condition of ischemic extremity muscular discomfort induced by exercise muscular discomfort induced by exercise and relieved by short periods of restand relieved by short periods of restmanifestation of PAD due to manifestation of PAD due to atherosclerosis atherosclerosis Consequence: serious lifestyle Consequence: serious lifestyle modificationsmodifications15% deteriorate and progress to critical 15% deteriorate and progress to critical limb ischemia limb ischemia
Conservative treatment for mild-Conservative treatment for mild-moderate diseasemoderate disease
Lifestyle modifications: smoking cessation, Lifestyle modifications: smoking cessation, diet diet
Lengthen pain-free and maximal walking Lengthen pain-free and maximal walking distance by walking exercise programdistance by walking exercise program
Strict Strict supervisedsupervised exercise regimen exercise regimen
Platelet Inhibitors: ASAPlatelet Inhibitors: ASA
reduces secondary events in pts with reduces secondary events in pts with atherosclerotic dx; improves graft patencyatherosclerotic dx; improves graft patencyHas NOT been shown to improve pain free Has NOT been shown to improve pain free walking distance (PFWD), maximal walking distance (PFWD), maximal walking distance (MWD) or symptoms in walking distance (MWD) or symptoms in pts with ICpts with ICNot indicated for symptoms of claudicationNot indicated for symptoms of claudicationDue to reduction of secondary eventsDue to reduction of secondary events all all pts w/ PAD should be on ASApts w/ PAD should be on ASA
Platelet Inhibitors: Clopidogrel Platelet Inhibitors: Clopidogrel (Plavix)(Plavix)
Antiplatelet agent; better than ASA in Antiplatelet agent; better than ASA in reducing secondary events in pts with reducing secondary events in pts with atherosclerosis atherosclerosis
CAPRIE trial: showed reduction in stroke, CAPRIE trial: showed reduction in stroke, MI, death MI, death
No evidence that symptoms of IC are No evidence that symptoms of IC are reduced with Plavixreduced with Plavix
VasodilatorsVasodilators
Former theory: Dilate BVFormer theory: Dilate BV more blood to more blood to ischemic limbischemic limbReality: Ischemic tissueReality: Ischemic tissue metabolic metabolic byproductsbyproducts maximal dilation of vessels maximal dilation of vessels distal to a lesiondistal to a lesionVasodilators cause proximal and parallel Vasodilators cause proximal and parallel vessels to dilatevessels to dilate steal phenomenon steal phenomenonVasodilatorsVasodilators decreased SVR decreased SVR decreased perfusion pressure decreased perfusion pressure
CCB (verapamil): increases PFWD and CCB (verapamil): increases PFWD and MWD in one study (Bagger et al)MWD in one study (Bagger et al)
No change in ABI’sNo change in ABI’s
CCB has another effect: changes oxygen CCB has another effect: changes oxygen extraction/utilization capacityextraction/utilization capacity improve improve efficiency of oxygen use in the extremityefficiency of oxygen use in the extremity
Pure Vasodilators not recommended for IC Pure Vasodilators not recommended for IC
Pentoxifylline (Trental)Pentoxifylline (Trental)
Methylxanthine derivative Methylxanthine derivative Improvement of RBC deformity, decreases blood Improvement of RBC deformity, decreases blood viscosity, platelet aggregation inhibition, viscosity, platelet aggregation inhibition, reduction in fibrinogen levelsreduction in fibrinogen levels2 studies: increased PFWD, as did placebo, with 2 studies: increased PFWD, as did placebo, with no change in pt quality of life/ subjective no change in pt quality of life/ subjective symptoms; symptoms; May wear off with long term useMay wear off with long term useMonitor drug levels and activity if pt is on other Monitor drug levels and activity if pt is on other methylxanthine derivatives (theophylline, methylxanthine derivatives (theophylline, aminophylline)aminophylline)
Cilostazol (Pletal)Cilostazol (Pletal)
Phosphodiesterase type III inhibitorPhosphodiesterase type III inhibitor inhibits cAMP phosphodiesteraseinhibits cAMP phosphodiesterase ↑cAMP↑cAMP platelet aggregation inhibitionplatelet aggregation inhibition and and ↑SMC relaxation↑SMC relaxation
↑↑HDL, ↓ triglyceridesHDL, ↓ triglycerides
↓↓SMC proliferation (in vitro studies only)SMC proliferation (in vitro studies only)
Large double blind trial: 100 mg po bid Large double blind trial: 100 mg po bid ↑MWD + subjective improvement↑MWD + subjective improvement
Cilostazol (Pletal)Cilostazol (Pletal)
Side effects: HA, GI c/o, palpitations, Side effects: HA, GI c/o, palpitations, ↑ HR↑ HR
Start at low dose (50mg qd)Start at low dose (50mg qd)
Contraindicated in pts with CHFContraindicated in pts with CHF
Liver metabolismLiver metabolism may reduce dose if pt may reduce dose if pt is on erythromycin, antifungals, SSRI, is on erythromycin, antifungals, SSRI, omeprazole omeprazole
Increases PFWD, MWD: Increases PFWD, MWD: Keep reasonable Keep reasonable expectationsexpectations
Naftidrofuryl (Praxilene)Naftidrofuryl (Praxilene)
Serotonin antagonist; vasodilatory Serotonin antagonist; vasodilatory properties and improved efficiency of properties and improved efficiency of aerobic mechanism aerobic mechanism
Increases PFWD, not MWDIncreases PFWD, not MWD
GI c/o GI c/o
Not available in US, used frequently in Not available in US, used frequently in EuropeEurope
improves availability of substrates required improves availability of substrates required for energy production, increasing for energy production, increasing efficiency of Kreb cycleefficiency of Kreb cycle
Significant PFWD increase and subjective Significant PFWD increase and subjective improvement shownimprovement shown
Carnitine supplements available in health Carnitine supplements available in health food stores food stores
Use not currently scientifically supportedUse not currently scientifically supported
Levocarnitine Levocarnitine
Chelation therapy Chelation therapy
Binds with CaBinds with Ca+2+2 prevents progression of/ prevents progression of/ reverses atherosclerotic dxreverses atherosclerotic dx
EDTA EDTA
Data not convincing Data not convincing
Requires monitoring of Chemistry and Requires monitoring of Chemistry and hematology hematology
May function as an Antioxidant May function as an Antioxidant
New FDA study to evaluate its benefitNew FDA study to evaluate its benefit
Currently not recommended for IC Currently not recommended for IC
Arginine Arginine
aa, precursor for nitric oxide formationaa, precursor for nitric oxide formation
May May ↑PFWD, ↑ MWD↑PFWD, ↑ MWD
Further studies neededFurther studies needed
Available as oral supplement in most Available as oral supplement in most health food stores health food stores
Not currently recommended for ICNot currently recommended for IC
Ginkgo bilobaGinkgo biloba
Meta-analysis of randomized double-blind, Meta-analysis of randomized double-blind, placebo controlled trials comparing placebo controlled trials comparing Ginkgo Ginkgo biloba biloba with placebowith placebo
Ginkgo bilobaGinkgo biloba ↑PFWD, ↑MWD↑PFWD, ↑MWD
GI c/o most commonGI c/o most common
More large scale trials neededMore large scale trials needed
BuflomedilBuflomedil
Vasoactive drug, platelet inhibition, Vasoactive drug, platelet inhibition, improves RBC deformityimproves RBC deformity
Improves efficiency of muscle cell Improves efficiency of muscle cell metabolismmetabolism
Improved PFWD, MWD (Trubestein et al)Improved PFWD, MWD (Trubestein et al)
Side effects: GI c/o, HA, dizziness, Side effects: GI c/o, HA, dizziness, erythema and pharyngitiserythema and pharyngitis
Not available in US (Europe and LA)Not available in US (Europe and LA)
KetanserinKetanserin
Serotonin S-2 receptor antagonistSerotonin S-2 receptor antagonist
Extensive testing in EuropeExtensive testing in Europe
One study: no improvement of PFWDOne study: no improvement of PFWD
Not currently recommended Not currently recommended
Niacin and LovastatinNiacin and Lovastatin
Combined positive effects on total Combined positive effects on total cholesterol, LDL, triglycerides, and HDL’s, cholesterol, LDL, triglycerides, and HDL’s, combined with reduction in fibrinogen combined with reduction in fibrinogen levelslevels improve IC symptoms improve IC symptoms
Inositol niacinate (niacin derivative)Inositol niacinate (niacin derivative) improved PFWD in small studyimproved PFWD in small study
GI c/o, flushingGI c/o, flushing
Awaiting large-scale results Awaiting large-scale results
SummarySummary
Numerous and at time serious lifestyle Numerous and at time serious lifestyle consequences of ICconsequences of ICFDA approved treatment for IC: FDA approved treatment for IC: pentoxifylline (Trental) and cilostazol pentoxifylline (Trental) and cilostazol (Pletal)(Pletal)Lifestyle modification is keyLifestyle modification is keyOnly nonoperative tx consistently shown to Only nonoperative tx consistently shown to lengthen MWD and PFWD is a lengthen MWD and PFWD is a supervised exercise regimensupervised exercise regimen