Title Prevencija i liječenje postpunkcijske glavobolje peroralnom primjenom teofilina
Title (english) Prevention and treatment of postdural puncture headache with peroral thepohyline
Author Krešimir Čaljkušić
Mentor Ivo Lušić (mentor)
Committee member Marina Titlić (predsjednik povjerenstva)
Committee member Mladen Boban (član povjerenstva)
Committee member Petar Filipović Grčić (član povjerenstva)
Granter University of Split School of Medicine Split
Defense date and country 2013, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Neurology
Universal decimal classification (UDC ) 616 - Pathology. Clinical medicine
Abstract Lumbalna punkcija (LP) uobičajena je neurološka procedura koja se rabi u dijagnostičke i u terapijske svrhe. Postpunkcijska glavobolja (PPG) razmjerno je česta popratna pojava lumbalne punkcije čija se incidencija kreće u rasponu od 30% do 50% kod dijagnostičkih ili terapijskih lumbalnih punkcija, dok se tijekom provođenja epiduralne anestezije ukoliko se dogodi „incidentalni“ ubod dure učestalost povećava do 80%. Upravo tako velika učestalost tog problema u svakodnevnoj kliničkoj neurološkoj praksi opravdava težnju brojnih kliničkih studija posvećenih prevenciji PPG-a, ili smanjenju njezina intenziteta. Češće navođeni pripravci s potencijalnim učinkom na učestalost i intenzite PPG su lijekovi iz skupine metilksantina, posebice teofilin. Teofilin bi se kao lijek s dobro poznatim farmakodinamskim i farmakokinetskim svojstvima te predvidivim nuspojavama mogao vrlo jednostavno primjenjivati u prevenciji i/ili liječenju PPG-a, a s obzirom na jednostavnost primijene tog lijeka PPG bi bilo moguće liječiti i u izvanbolničkim uvjetima. Hipotetski, teofilin kompetitivnom neselektivnom inhibicijom fosfodiesteraze, neselektivnim antagonističkim djelovanjem na adenozinske receptore te interferiranjem s unosom kalcija u sarkoplazmatsku mrežicu smanjuje kompenzatornu venodilataciju. Osim toga, teofilin stimuliranjem natrijsko-kalijske pumpe uzrokuje povećano stvaranje likvora. Prikazanim mehanizmima teofilin djeluje na dva osnovna prihvaćena patofiziološka mehanizma nastanka PPG-a, što bi trebalo rezultirati rjeđom pojavom i slabijim intenzitetom PPG-a.
Provedeno je dvostruko slijepo randomizirano istraživanje u skupini hospitaliziranih pacijenata u kojih je postavljena indikacija za dijagnostičku lumbalnu punkciju (LP) zbog sumnja na demijelinizacijsku bolest središnjeg ili perifernog živčanog sustava. Ispitivana je populacija oba spola (27 žena i 12 muškaraca) u dobi od 18 do 50 godina. Ispitanici su, nakon potpisivanja informiranog pristanka, randomizirani u dvije skupine. Njih 17 je (44%) primalo placebo,a 22 (56%) su peroralno primala 300 mg teofilina u obliku tablete s produljenim oslobađanjem dvaput na dan tijekom pet dana uzastopno. Ispitanici su četiri puta dnevno , počevši od prvog dana 30 minuta prije LP-a , procjenjivali intenzitet eventualne glavobolje prema vizualno-analognoj ljestvici (VAS-u). Osim toga, ispitanici su bilježili eventualnu pojavu mučnine, i to prema VAS-u te prema upitniku Oweral nausea index
( ONI).
Osim što je prvog dana praćenja zabilježena statistički značajna razlika u učestalosti glavobolje između dviju ispitnih skupina, tijekom daljnjeg praćenja nije zamijećena statistički značajna razlika između tih skupina. U objema je ispitivanim skupinama uočena razlika u intenzitetu glavobolje petog dana u odnosu prema drugom, trećem i četvrtom danu praćenja. To opažanje s jedne strane tumačimo mogućim spontanim povlačenjem simptoma, što se i inače opaža u nekih bolesnika, no u velikog dijela ispitanika smanjenje intenziteta PPG-a povezujemo s činjenicom da je protokol istraživanja dopuštao uzimanje nesteroidnih analgetika ako bude potrebno. Nije uvrđena statistički značajna razlika u broju ispitanika s mučninom s obzirom na primijenjenu terapiju mjereno prema VAS ljestvici, a ni statistički značajna razlika u broju ispitanika s mučninom s obzirom na primijenjenu terapiju mjereno prema ONI ljestvici. U ispitanika koji su osjećali mučninu nije utvrđena statistički značajna razlika u njezinu intenzitetu mjereno prema VAS ljestvici, a ni prema ONI ljestvici s obzirom na primijenjenu terapiju.
Rezultati prikazanog istraživanja ne potvrđuju tezu o učinkovitosti peroralno primijenjenog teofilina u prevenciji pojave PPG-a ni tezu o njegovoj učinkovitosti u liječenju postojećeg PPG-a i prateće mučnine.
Abstract (english) Lumbar puncture (LP) is a common neurological procedure used for the diagnostic and therapeutic purposes. Postdural puncture headache (PDPH) is a relatively common side effect of lumbar puncture with an incidence ranging from 30% to 50% in the case of a diagnostic or therapeutic lumbar puncture. However, if “incidental” dural jab happens, the incidence rises to 80% during epidural anesthesia . A high frequency of this problem in clinical neurology justifies numerous clinical studies devoted to prevention of PDPH or reduction of its intensity.
One of the frequently investigated drugs is theophylline, a drug from the group of methylxanthines. Theophylline is a drug with well-known pharmacodynamic and pharmacokinetic properties, including its side effects, so it could be easily applied in the prevention and / or treatment of PDPH. Since it is very easy to apply theophylline orally, it can be used for PDPH treatment in outpatient facilities. Our research was conducted with a group of patients hospitalized in the Department of Neurology, Split University Hospital during the period from 1st May of 2011 untill 31st March of 2012. The indication for performing diagnostic LP was suspected demyelinating disease of the central or peripheral nervous system. There have been investigated subjects of both genders (27 females and 12 males) aged 18-50. Subjects were randomized into two groups. 17 (44%) patients were receiving placebo, whereas 22 (56%) were receiving orally 300 mg of theophylline as the extended release tablets twice a day for five consecutive days. Neither the patients nor the doctors who were prescribing the drug (or placebo), as well as researchers who have noted the results of the poll were aware of randomization until the end of the study. Using visual analog scale (VAS) in the range 0-10, subjects have been estimating its headache intensity four times a day - starting from 30 minutes before LP – for the following five days. Furthermore, subjects noted the potential occurrence of nausea using VAS and the "Oweral nausea index" questionnaire (ONI).
The statistically significant difference between these groups, with regard to the headache frequency, was found only for the first day of treatment. During the follow-up, there were no statistically significant differences between the same groups.
In both groups, there was a difference in a headache intensity on the fifth day compared to the second, third and the fourth day. This could be due to the spontaneous withdrawal decreased intensity of PDPH associated with the intake of nonsteroid antiinflamatory drugs, which were allowed by the protocol.
Statistically significant difference was not found in the number of subjects with nausea with regard to applied therapy as indicated by VAS.Anyway, there was a significant difference found in the number of subjects with nausea with regard to applied therapy as indicated by the ONI scale. In subject who reported nausea, there was no significant difference in its intensity indicated by VAS or ONI scale with regards to applied therapy. The results do not confirm the hypothesis that orally administered theophylline is effective in prevention of PDPH. Also, the research does not verify the effectiveness of the thesis in treating existing PDPH and accompanying nausea.
Keywords
Glavobolja nakon duralne punkcije -- prevencija i kontrola
Teofilin
Keywords (english)
Post-Dural Puncture Headache -- prevention and control
Theophylline
Language croatian
URN:NBN urn:nbn:hr:171:415943
Study programme Title: Basic and clinical medical sciences Study programme type: university Study level: postgraduate Academic / professional title: magistar/magistrica znanosti (magistar/magistrica znanosti)
Type of resource Text
File origin Born digital
Access conditions Open access
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Created on 2023-06-05 07:54:12