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Vpliv lokalnih anestetikov na sklepni hrustanec v kolenu
Ravnihar, Klemen (Avtor), Drobnič, Matej (Mentor) Več o mentorju... Povezava se odpre v novem oknu, Marš, Tomaž (Komentor)

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Izvleček
Uvod Znotraj-sklepne aplikacije lokalnih anestetikov so v medicini zelo pogoste in so veljale za varne, vse dokler se niso pojavili opisi okvare hrustanca, t.i. hondrolize, ki je bila najverjetneje povezana z njihovo uporabo. Izhajajoč iz opisanih primerov hondrolize, so bile opravljene številne in vitro raziskave, ki so potrdile, da že kratkotrajna izpostavljenost lokalnim anestetikom lahko povzroči moteno delovanje in smrt hondrocitov. Predvidevamo, da v okolju znotraj sklepa delujejo dejavniki, ki zmanjšujejo hondrotoksični učinek lokalnih anestetikov, saj je pojavnost hondrolize v klinični praksi zelo nizka. Z našo raziskavo, ki je potekala v štirih povezanih delih, smo poskušali te dejavnike ovrednotiti in tako potrditi, da klinična uporaba lokalnih anestetikov za enkratno aplikacijo pri artroskopiji kolena v lokalni anesteziji ali kot enkratna protibolečinska injekcija, nima škodljivega učinka na sklepni hrustanec v kolenu. Metode 1) Analizirali smo podatke 49 pacientov, pridobljenih med postopki za zdravljenje hrustančnih lezij v kolenu z implantacijo gojenih avtolognih hondrocitov. Primerjali smo celično viabilnost, populacijsko podvojevanje ter morfologijo celic v biopsijah in primarnih kulturah med različnimi oblikami anestezije (splošna, spinalna, lokalna) pri artroskopskem odvzemu hrustančnih biopsij. 2) Določili smo znotraj-sklepno koncentracijo lokalnega anestetika pri 10 bolnikih. Med rutinsko artroskopijo kolena v lokalni anesteziji, pri kateri smo v sklepno votlino injicirali/infiltrirali 2% lidokain, smo odvzeli vzorce sinovialne tekočine. V vzorcih smo z metodo masne spektrometrije določili koncentracijo lidokaina, ki je prisotna v sklepu 10-15 minut po znotraj-sklepni aplikaciji. 3) Pri obdukcijah na sodni medicini smo iz zdravih kolen 10 mrtvih donorjev odvzeli 27 kostno-hrustančnih eksplantov. Eksplante smo inkubirali v različnih časovnih intervalih (30 min, 2 uri in 24 ur) s standardno 2% raztopino lidokaina, s koncentracijo lokalnega anestetika izmerjeno v drugem delu raziskave (0,04%) in v kontrolni skupini z medijem za gojenje celic. Določili smo razlike v viabilnosti hondrocitov med skupinami s celično analizo hrustančnega tkiva s konfokalnim laserskim mikroskopom. 4) Določali smo vpliv lidokaina na degenerativno spremenjeni hrustanec. Pri 10 bolnikih predvidenih za vstavitev totalne endoproteze (TEP) kolena smo tik pred posegom v sklep aplicirali lokalni anestetik, nato pa smo v degenerativno spremenjenem hrustancu na reseciranih površinah napravili analizo viabilnost hondrocitov s pomočjo konfokalnega laserskega mikroskopa ter meritve primerjali z viabilnostjo hondrocitov pri 9 bolnikih brez dodanega lokalnega anestetika. Rezultati 1) Pri analizi celic v hrustančnih biopsijah nismo našli razlik med različnimi oblikami anestezije. Viabilnost celic v biopsijah in njihov potencial za rast in razmnoževanje nista bila pomembno zmanjšana po izpostavitvi lidokainu pri artroskopiji v lokalni anesteziji. 2) V kolenskem sklepu smo izmerili izrazito nižje koncentracije lidokaina (povprečno 225 mg/ml - 0,02%), kot smo jo pričakovali glede na ocenjeno volumsko razporeditev. 3) Nizka izmerjena koncentracija lidokaina pri kratkotrajni izpostavljenosti ni vplivala na viabilnost celic v hrustančnih eksplantih zdravih kolen in vitro. 4) Izpostavljenost degenerativno spremenjenega hrustanca lokalnemu anestetiku in vivo ni pomembno znižala celične viabilnosti v primerjavi s kontrolno skupino brez anestetika. Zaključek Nobena od raziskav v sklopu doktorske naloge ni potrdila pomembnega škodljivega vpliva enkratne znotraj-sklepne aplikacije lidokaina ali škodljivosti kratkotrajne izpostavljenosti sklepnega hrustanca v kolenu lidokainu. Z rezultati smo pokazali, da v fiziološkem okolju kolenskega sklepa delujejo procesi, ki ščitijo sklepni hrustanec pred toksičnim učinkom lokalnih anestetikov. Ti procesi najverjetneje vključujejo pomembno znižanje sklepne koncentracije lokalnega anestetika hitro po njegovi aplikaciji in omejeno prehajanje anestetika skozi vrhnje plasti intaktnega sklepnega hrustanca.

Jezik:Slovenski jezik
Ključne besede:sklepni hrustanec, lokalni anestetik, lidokain, lokalna anestezija, hondroliza, artroskopija, artroza
Vrsta gradiva:Doktorsko delo/naloga (mb31)
Organizacija:MF - Medicinska fakulteta
Leto izida:2018
Število ogledov:726
Število prenosov:404
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Sekundarni jezik

Jezik:Angleški jezik
Naslov:Effect of local anesthetics on articular cartilage in the knee
Izvleček:
Introduction Intra-articular application of local anesthetics is a common procedure in clinical medicine. It was considered safe until the first reports of unusual acute postoperative degeneration and degradation of articular cartilage, so called chondrolysis, emerged in the literature. Chondrolysis was typically occurring after arthroscopic surgery followed by postoperative pain management with continuous infusion of local anesthetics. Based on those reports, many in vitro studies showed harmful effect of local anesthetics on the articular cartilage. Even short term exposure caused chondrocyte dysfunction and death. As there are no known reports on chondrolysis after knee arthroscopy in local anesthesia or after single intra-articular injection for pain management, we hypothesized that certain chondroprotective factors exist in the natural environment, that protect articular cartilage from toxic effect caused by local anesthetics. Presented thesis was designed as four interconnecting experiments combining in vivo clinical data and in vitro laboratory simulations with intention to show that clinical use of single application of local anesthetic for knee arthroscopy or single analgesic injection have no harmful effect on the articular cartilage of the knee. Methods 1) Data of 49 patients that were treated for isolated cartilage lesions in the knee with autologous chondrocyte implantation were retrospectively analyzed. Bioptic samples of cartilage were harvested from their knees with arthroscopy under general, spinal, and local anesthesia. The three anesthesia groups were compared for cell viability, population doublings, and chondrocyte morphologic properties in biopsies and also in cell cultures. 2) Intra-articular concentration of lidocaine was determined in 10 patients during knee arthroscopy in local anesthesia. They received an intra-articular injection/infiltration of 2% lidocaine ten to fifteen minutes prior to the procedure. With the introduction of the arthroscope, joint liquid samples were aspirated and then analyzed for the concentration of lidocaine with mass spectrometry. 3) 27 osteochondral explants were harvested from the healthy knees of 10 donors during forensic autopsies. The explants were incubated for different time intervals (30 min, 2h and 24h) in standard 2% concentration of lidocaine, in the concentration measured in the second subexperiment of the study (0.04%) and in the cell culture medium (control). The differences in viability of chondrocytes among groups were evaluated on confocal laser microscope. 4) The effect of lidocaine on degenerated cartilage was determined in osteoarthritic knees. 10 patients scheduled for total knee replacement received an intra-articular injection of 2% lidocaine 10 to 15 minutes prior to the procedure. During surgery, osteochondral explants were harvested and analyzed for the viability of chondrocytes under confocal laser microscope. The results were compared to control group of 9 patients without preoperative lidocaine injection. Results 1) No differences in cell viability, growth potential, and morphology of cells in cartilage biopsies and chondrocyte cell cultures among different types of anesthesia were found. 2) The concentration of lidocaine in knee aspirates was significantly lower than the original concentration infiltrated in the knee (on average 225 mg/ml, 0,02%); it was also lower than we would expect solely on the basis of volume distribution. 3) In vitro short term exposure to the reduced concentration of lidocaine had no influence on chondrocyte viability in healthy cartilage explants. 4) Viability of chondrocytes in degenerated cartilage in the knees treated with preoperative 2% lidocaine injection was not significantly reduced in comparison to the control group. Conclusion None of the subexperiments of this study demonstrated a harmful effect of single intra-articular knee administration of lidocaine or short term exposure to lidocaine on articular cartilage of the knee. According to our results there are intra-articular mechanisms present that diminish local anesthetic toxicity to the cartilage in the physiologic conditions. The most important factors appear to be a significant reduction of local anesthetic concentration shortly after its intra-articular application and limited penetration of local anesthetic through the intact superficial cartilage layers.

Ključne besede:articular cartilage, local anesthetic, lidocaine, local anesthesia, chondrolysis, arthroscopy, arthritis

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