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Gentamicin je aminoglikozidni antibiotik s toksičnim delovanjem na ledvice, slušni in ravnotežni organ, kar predstavlja ključno terapevtsko omejitev pri njegovi uporabi. Večje tveganje za pojav neželenih učinkov je povezano s povišanimi minimalnimi serumskimi koncentracijami gentamicina nad priporočeno mejo. Z retrospektivno raziskavo na Kliničnem oddelku za otroško kirurgijo in intenzivno terapijo, Kirurška klinika, Univerzitetni klinični center Ljubljana, smo želeli analizirati terapevtsko spremljanje koncentracij gentamicina, skladnost s priporočili ter dejavnike, ki vplivajo na koncentracije izven priporočenega območja. Vključili smo otroke, stare manj kot 14 let, ki so se z gentamicinom zdravili na oddelku v letu 2015 in so imeli v času zdravljenja vsaj enkrat izmerjeno minimalno serumsko koncentracijo gentamicina (cmin). Analizirali smo 69 bolnikov, od tega 44,9% otrok ženskega spola. Devet otrok se je z gentamicinom zdravilo večkrat, zato smo vsak primer zdravljenja obravnavali ločeno. Skupno smo obravnavali 81 primerov zdravljenja, ki smo jih razdelili v starostne skupine. Opravljenih je bilo 146 meritev cmin. Ugotovili smo, da se referenčno območje za cmin gentamicina na Kliničnem oddelku za otroško kirurgijo in intenzivno terapijo razlikuje od mej, predpisanih v priporočilih, in opredeljuje tudi spodnjo mejo za cmin, kar ni v skladu s podatki iz literature. Delež previsokih cmin glede na njihovo območje je bil 27,2%, glede na referenčno območje iz priporočil pa 49,4%. Največji delež previsokih cmin je bil pri novorojencih. Čas odvzema prvega vzorca za določanje cmin in pogostost merjenja nista jasno definirana. Spremembe v režimu terapije so bile izvedene pri 25% vseh otrok s previsokimi cmin, uspešnost le-teh je bila 10%. Neskladnost referenčnega območja je vzrok za manjše število izvedenih ukrepov v primeru neustreznih koncentracij cmin. Nefrotoksičnost zaradi zdravljenja z gentamicinom je bila ugotovljena pri 4 od 81 otrok, neželenih učinkov na slušni in ravnotežni organ ni bilo zabeleženih. Dokazali smo značilno povezavo med previsokimi vrednostmi cmin gentamicina ter starostjo otrok, vrsto obravnave in ledvično funkcijo. Tveganje za previsoke cmin je največje pri nedonošenem ali donošenem novorojencu, ki je obravnavan na intenzivnem oddelku in ima oslabljeno ledvično funkcijo. Pri teh kliničnih primerih je potrebno skrbnejše odmerjanje in spremljanje ledvične funkcije, pogostejše izvajanje terapevtskega spremljanja koncentracij ter ustrezno ukrepanje v primeru previsokih cmin. Gentamicin is an aminoglycoside antibiotic that is oto- and nephrotoxic which limits its therapeutic application. The increased risk of these adverse reactions is associated with elevated serum concentrations of gentamicin above a certain limit.With a retrospective study at the Department of Paediatric Surgery and Intensive Care, Division of Surgery, Ljubljana University Medical Centre, we wanted to analyse gentamicin therapeutic monitoring, compliance with recommendations and factors that influence concentrations outside the recommended area. We included children aged less than 14 years who were treated with gentamicin in the department in 2015 and had at least once measured the minimum serum gentamicin concentration (cmin). We analysed 69 patients and 44,9% were female. Nine children were treated with gentamicin several times, so each case of treatment was considered separately. Altogether, 81 cases were considered, which we divided into age groups. There were 146 measurements of cmin. We found that the reference area for cmin of gentamicin at the Department of Paediatric Surgery and Intensive Care differs from guidelines and also defines the lower limit for the cmin, which is not in accordance with the data from the literature. The portion of too high cmin in relation to their reference area was 27,2%, and 49,4% according to the reference area in the guidelines. The highest portion of too high cmin was found in newborns. Also, the time of collection of the first sample to determine cmin and the frequency of measurement are not clearly defined. After too high cmin were determined, interventions were performed in only 25% of the cases and only 10% of them were successful. The inconsistency of the reference area is the reason for the smaller number of interventions undertaken. Nephrotoxicity due to gentamicin treatment was found in 4 out of 81 cases and no adverse effects on the auditory organs and organs of balance were recorded. We have proven a significant relationship between the high values of cmin and the age of patients, the type of treatment and the renal function value. The risk of too high cmin is the highest in the newborn infant who is treated in the intensive care unit and has impaired renal function. In these cases, more careful dosing and monitoring of renal function is required as well as more frequent conduction of therapeutic monitoring and appropriate intervention in the case of too high cmin. |
