10. PERIFERNA ARTERIJSKA BOLEZEN Aleš Blinc
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1 10. PERIFERNA ARTERIJSKA BOLEZEN Aleš Blinc Periferna arterijska bolezen (PAB) je pri bolnikih s sladkorno boleznijo dva- do štirikrat pogostejša kot pri splošni populaciji, njen potek je hitejši in malignejši. Med bolniki, ki zaradi kritične ishemije utrpijo amputacijo stopala, je vsaj polovica diabetikov. S pravočasnim prepoznavanjem PAB in ustreznim zdravljenjem je mogoče potek bolezni izboljšati. PRIPOROČILA Diagnoza 1. Določanje gleženjskega indeksa kot temeljno objektivno diagnostično metodo za prepoznavanje PAB svetujemo v sklopu pregleda nog diabetikom po 50. letu starosti in vsem diabetikom z vsaj še enim dejavnikom tveganja za srčno-žilne bolezni (1). (E*) 2. Tlak na haluksu služi za prepoznavanje PAB pri preiskovancih z nestisljivimi golenskimi arterijami, pri katerih vrednotenje gleženjskega indeksa ni mogoče (2, 3). (B) 3. Slikovno diagnostiko perifernih arterij opravimo, kadar načrtujemo revaskularizacijski poseg. Le-ta je indiciran pri bolnikih z omejujoče kratko klavdikacijsko razdaljo in pri bolnikih s kritično ishemijo uda, ki se kaže kot ishemična bolečina med mirovanjem ali ishemična razjeda (1, 4, 5). (E*) 4. Za slikovno diagnostiko perifernih arterij so primerne metode ultrazvočna preiskava žilja (6, 7), magnetnoresonančna angiografija (8, 9), angiografija z računalniško tomografijo (10, 11) in digitalna subtrakcijska angiografija (6, 9-12) (A). Digitalno subtrakcijsko angiografijo uporabljamo predvsem v kombinaciji z znotrajžilnimi revaskularizacijskimi posegi (1, 4, 5). (E*) Ukrepanje 5. Vsi bolniki s PAB potrebujejo za zmanjšanje tveganja aterotrombotičnih zapletov nefarmakološke ukrepe (nekajenje, gibanje, ustrezna prehrana, uravnavanje telesne teže) in farmakološke ukrepe (antiagregacijsko zdravljenje, antihipertenzivno in lipolitično zdravljenje) po smernicah za bolnike z izraženo srčno-žilno boleznijo (1, 4, 5, 13, 14, 15). (E*) 6. Temeljno zdravljenje kritične ishemije uda je revaskularizacijski poseg (16, 17). (B) 7. Parenteralno zdravljenje z iloprostom je možno pri bolnikih s kritično ishemijo uda, ki niso primerni za revaskularizacijski poseg (18) (A), vendar je uspešnost zdravljenja omejena na majhen odstotek bolnikov (1, 18). (E*) UTEMELJITEV
2 Vsem bolnikom s sumom na PAB vzamemo anamnezo in jih klinično pregledamo. Poudarek kliničnega pregleda je na tipanju perifernih pulzov, saj dobro tipni distalni pulzi izključujejo hemodinamsko pomembno PAB (1, 4, 5). Temeljna objektivna preiskava za potrditev suma na PAB, ki jo praviloma opravimo že na primarni ravni zdravstva v sklopu pregleda nog pri diabetikih, je merjenje sistoličnega arterijskega tlaka v gležnju in primerjava s tlakom na nadlakti (1, 4, 5, 19). Manšeto sfigmomanometra namestimo ležečemu bolniku nad gleženj in z uporabo Dopplerjevega detektorja izmerimo sistolični tlak v arteriji tibialis posterior in arteriji tibialis anterior, nato izmerimo tlak na obeh nadlakteh. Višji sistolični tlak v vsakem gležnju primerjamo z višjim sistoličnim tlakom na nadlakti, kar imenujemo gleženjski indeks. Normalno je arterijski tlak v gležnju enak ali večji od tlaka na nadlakti. Po dogovoru vrednotimo kot normalen rezultat gleženjski indeks od 0,91 do 1,30. Gleženjski indeks 0,90 ali manj je dokaz PAB (1, 19). Čim nižji je gleženjski indeks, tem bolj napredovala je PAB. Vrednosti gleženjskega indeksa pod 0,40 so znanilci kritične ishemije, pri čemer so absolutne vrednosti perfuzijskih tlakov v gležnju nižje od mmhg (1, 4). Neinvazivno merjenje gleženjskega tlaka odpove pri nestisljivih golenskih arterijah zaradi mediokalcinoze, ki je pogosta pri bolnikih s sladkorno boleznijo ali napredovalim ledvičnim popuščanjem. Pri vrednosti gleženjskega indeksa več kot 1,30 je za opredelitev PAB uporabno pletizmografsko merjenje perfuzijskega tlaka na palcu noge, saj mediokalcinoza ne sega v arterije prstov. Tlak v arterijah prstov je za približno 10 mmhg nižji od tlaka v gležnju. O kritični ishemiji govorimo, kadar je tlak na palcu noge nižji od 30 mmhg, vrednosti nad 50 mmhg pa kritično ishemijo izključujejo (1, 4, 5). Skozikožna oksimetrija sodi med preiskave mikrocirkulcije in je uporabna predvsem pri diagnostiki kritične ishemije uda ob izraženi mediokalcinozi golenskih arterij z lažno visokim gleženjskim indeksom (1, 4, 5). Po revaskularizacijskem posegu na perifernih arterijah diabetikov ima skozikožna oksimetrija veliko večji napovedni pomen glede ohranitve uda kot gleženjski indeks (20). Skozikožna oksimetrija je lahko uporabna tudi pri določanju ravni amputacije ob nerekonstruktibilni prizadetosti arterij z distalno gangreno uda (1-3). Dokaj zanesljivo lahko izključimo kritično ishemijo uda in napovemo celjenje razjede, če delni tlak kisika v podkožju presega 40 mmhg (1, 4, 5). Morfološke preiskave arterij so pri bolnikih s PAB indicirane, ko ishemija uda bolnika pomembno ovira pri hoji ali kadar povzroča kritično ishemijo z ishemično bolečino med mirovanjem ali razjedo. Zlati standard je digitalna subtrakcijska angiografija, ki ob ustreznem pristopu v arterijo omogoča takojšnje nadaljevanje diagnostičnega postopka z znotrajžilnimi posegi (1, 4, 5, 21). Kadar ne načrtujemo takojšnjega znotrajžilnega revaskularizacijskega posega ali kadar se želimo izogniti arterijski punkciji, opravimo ultrazvočno preiskavo arterij, angiografijo z računalniško tomografijo ali magnetnoresonančno angiografijo (1, 4, 5). Zdravljenje PAB je sestavljeno iz dveh osnovnih skupin ukrepov: (a) sistemskega preprečevanja aterotrombotičnih zapletov in (b) lokalno usmerjenega zdravljenja klavdikacijskih simptomov ali kritične ishemije uda (1, 4, 5, 22).
3 Preprečevanje aterotrombotičnih zapletov. Nefarmakološki ukrepi za zmanjševanje srčnožilnih zapletov obsegajo predvsem nekajenje, uživanje zdrave hrane, uravnavanje telesne teže in v stadiju intermitentne klavdikacije tudi redno telesno dejavnost, najbolje z intervalno hojo (1, 4, 5, 13, 14, 23). Antiagregacijsko zdravljenje z aspirinom v majhnem odmerku ( mg/dan) je indicirano pri vseh diabetikih s PAB, če ne obstaja izrecna kontraindikacija (1, 4, 5, 24). Alternativno antiagregacijsko zdravilo je klopidogrel 75 mg/dan (1, 4, 25). Omeniti je treba, da je antiagregacijsko zdravljenje z aspirinom pri diabetikih manj učinkovito kot v splošni populaciji (26). Aspirin ni učinkovito preprečeval aterotrombotičnih zapletov pri osebah z znižanim gleženjskim indeksom brez klavdikacijskih težav (27). Lipolitično zdravljenje s statini je indicirano, da dosežemo raven skupnega holesterola 4,5 mmol/l in LDL-holesterola 2,5 mmol/l (1, 5, 14, 22). Obstajajo dokazi da so koristne še nižje vrednosti (1,14, 22, 28). Antihipertenzivno zdravljenje je indicirano z namenom, da pri diabetikih s PAB dosežemo raven krvnega tlaka 130/80 mmhg (1, 14). Za zmanšanje srčno-žilnih zapletov je priporočljiva uporaba lipofilnih zaviralcev angiotenzinske konvertaze, zlasti ramiprila in perindoprila (29, 30). Blokatorji beta niso kontraindicirani pri stabilni PAB, vendar niso prva izbira antihipertenzivnega zdravljenja (1, 22) in jih uporabljamo predvsem pri bolnikih s pridruženo koronarno boleznijo (1, 13, 22). Krvnega tlaka ne zmanjšujemo agresivno pri bolnikih s kritično ishemijo uda pred opravljenim revaskularizacijskim posegom (1, 4, 5). Pojavljajo se poročila, da je za preprečevanje srčno-žilnih zapletov, vključno z napredovanjem PAB, pomembno dobro uravnavanje glikemije (31-34), vendar dokazi niso enoznačni, zato na tem področju ni konsenza (35). Zdravljenje klavdikacijskih simptomov ali kritične ishemije uda. Za zdravljenje klavdikacijskih težav, kadar sposobnost hoje ni omejujoče majhna, je osnovni ukrep intervalni trening hoje (1, 21, 23). Številne randomizirane študije so dokazale, da intervalni mišični trening poveča razdaljo, ki jo bolniki prehodijo brez bolečine v povprečju za 100 do 150 odstotkov, izboljšuje pa tudi kakovost življenja. Za doseganje takšnih učinkov je potrebno vaditi od 35 do 50 minut tri- do petkrat na teden vsaj šest mesecev. Vadba je sestavljena iz intervalov hoje z individualno prilagojeno hitrostjo, ki po 3 do 5 minutah izzovejo zmerno bolečino v mečih, in intervalov počitka, med katerimi bolečina povsem popusti. Za uspešno izvajanje intervalnega mišičnega treninga sta potrebni dobra motiviranost bolnikov in tudi dokaj ohranjena telesna zmogljivost (23). Ker večini bolnikov ne moremo zagotoviti nadzorovanega programa vadbe, jim svetujemo, da hodijo v ustrezni, udobni obutvi in hojo prekinjejo, ko zaznajo zmerno bolečino v mečih. Odmori naj bodo dolgi toliko časa, da mišični simptomi povsem popustijo, kar se običajno zgodi po nekaj minutah. Farmakološko zdravljenje intermitentne klavdikacije je manj učinkovito od intervalnega mišičnega treninga in prihaja v poštev predvsem pri bolnikih, ki ne morejo učinkovito izvajati vadbe (19, 21). Pri nas je registriran pentoksifilin, ki ima statistično značilne, vendar skromne učinke na klavdikacijsko razdaljo. Revaskularizacijski posegi so indicirani pri bolnikih z omejujoče kratko klavdikacijsko razdaljo in pri bolnikih s kritično ishemijo uda, ki se kaže kot ishemična bolečina med mirovanjem ali ishemična razjeda (1, 4, 5). Revaskularizacijske posege delimo v znotrajžilne posege, ki so doživeli velik razmah v zadnjih desetletjih, in klasične kirurške revaskularizacijske posege, med katerimi je najpomembnejši žilni obvod. Pri izbiri načina
4 revaskularizacije se opiramo na morfologijo žilnih okvar, pogosto pa tudi na izkušnje terapevtov v posamezni zdravstveni ustanovi (1, 4, 5, 21). Farmarmakološko zdravljenje kritične ishemije s prostanoidi prihaja v poštev tedaj, kadar revaskularizacijski posegi v makrocirkualciji niso izvedljivi in nam preostane le, da s podporo mikrocirkulaciji poskušamo preprečiti njeno dokončno odpoved, ki vodi v gangreno uda. V ta namen uporabljamo zlasti iloprost, ki je stabilnejši analog prostaciklina (1, 4, 18). Žal je uspešnost zdravljenja z iloprostom omejena na relativno majhen odstotek bolnikov (1, 4, 18), zato tovrstnega zdravljenja ne uporabljamo rutinsko (1, 4, 5). Literatura 1. ACC/AHA Practice Guidelines: Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease. ACC/AHA Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic). Available at: 2. Carter SA, Tate RB. Value of toe pulse waves in addition to systolic pressures in the assessment of severity of peripheral arterial disease and critical limb ischemia. J Vasc Surg 1996; 24: Carter SA, Tate RB. The value of toe pulse waves in determination of risks for limb amputation and death in patients with peripheral arterial disease and skin ulcers or gangrene. J Vasc Surg 2001; 33: The TASC working group. Management of peripheral arterial disease Transatlantic inter-society consensus. Critical limb ischemia. Int Angiol 2000; 19, Suppl 1: Blinc A, Šurlan M, Ključevšek T, Klokočovnik T, Kanič V, Lobnik A, Kozak M, Šabovič M, Poredoš P. Smernice za odkrivanje in zdravljenje periferne arterijske bolezni. Zdrav Vestn 2004; 73: Whelan JF, Barry MH, Moir JD. Color flow Doppler ultrasonography: comparison with peripheral angiography for the investigation of peripheral vascular disease. J Clin Ultrasound 1992; 20: devries SO, Huniak MG, Polak JF. Summary receiver operating characteristic curves as a technique for metaanalysis of the diagnostic performance of duplex ultrasonography in peripheral arterial disease- Acta Radiol 1996; 3: Baum RA, Rutter CM, Sunshine JH, Blebea JS, Blebea J, Carpenter JP, et al. Multicenter trial to evaluate vascular magnetic resonance angiography of the lower extremity. American College of Radiology Rapid Technology assessment Group. JAMA 1995; 274: Rofsky MA, Adelman MA. MR angiography in the evaluation of atherosclerotic peripheral artreial disease. Radiology 2000; 214: Rieker O, Düber C, Schmiedt W, von Zitzewitz H, Schweden F, Thelen M. Prospective comparison of CT angiography of the legs with digital subtraction angiography. AJR Am J Roentgeneol 1996; 166: Martin ML, Tay KH, Flak B, Fry PD, Doyle DL, Taylor DC, et al.multidetector CT angiography of the aortoiliac system and lower extremities: a prospective comparison with digital subttraction angiography. AJR Am J Roentgenol 2003; 180: Jaff MR. Lower extremity arterial disease. Diagnostic aspects. Cardiol Clin. 2002; 20: Third Joint Task Force of European and other Societies on Cardiovascular Disease in Clinical Practice. Executive summary - European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2003; 24: American Diabetes Association. Standards of medical care in diabetes Diabetes Care 2007; 30, Suppl 1: S Rydén L, Standl E, Bartnik M, Van den Berghe G, Betteridge J, de Boer MJ, et al. Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Eur Heart J 2007; 28: Durham JR, Horowitz JD, Wright JG, Smead WL. Percutaneous transluminal angioplasty of tibial arteries for limb salvage in the high risk diabetic patient. Ann Vasc Surg 1994; 8: Nasr MK,, McCarthy RJ, Hardman J, Chalmers A, Horrocks M. The increasing role of percutaneous transluminal angioplasty in the primary management of ctritical limb ischemia. Eur J Vasc Endovasc Surg 2002; 23: Loosemore T, Chalmers T, Dormandy J. A meta-analysis or fandomized placebo control trials in Fontaine stages III and IV peripheral occlusive arterial disease. Int Angiol 1994; 13:
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14. PERIFERNA ARTERIJSKA BOLEZEN
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