o:801 Faktori koji utiču na proces eliminacije benzodiazepina, kliničku sliku i ishod akutne intoksikacije benzodiazepinima kod osoba starije životne dobi Factors affecting benzodiazepines elimination, clinical presentation andoutcome in elderly people acutely poisoned with benzodiazepines : doctoral dissertation sr Cilj ove studije bio je da se analiziraju faktori koji utiču na proces eliminacije benzodiazepina, težinu kliničke slike, razvoj komplikacija, i ishod akutne intoksikacije kod osoba starije životne dobi. U istraživanju je učestvovalo 95 ispitanika oba pola koji su hospitalno lečeni u Klinici za toksikologiju Vojnomedicinske Akademije (VMA) u Beogradu. Planirano istraživanje je sprovedeno kao klinička opservaciona kohortna studija. Pacijenti su podeljeni u tri pod grupe, prema životnoj dobi (18-40 godina, 41-65 godina, ≥ 65 godina). Svaki pacijent koji je uključen u studiju praćen je u skladu sa kliničkom slikom, te detektovanim toksičnim koncentracijama benzodiazepina minimalno 48 sati, odnosno do završetka lečenja. U ovom istraživanju najčešće su intoksikacije bromazepamom, a poređenjem srednjih koncentracija bromazepama na prijemu među različitim dobnim grupama uočavamo da su u grupi starijih od 65 godina one nešto više, ali se statistički značajno ne razlikuju u odnosu na mlađe dobne grupe. Eliminacija benzodiazepina je analizirana poređenjem koncentracije lekova na prijemu i određivanjem procentualnog smanjenja koncentracije posle 24 i 48 sati. Dominantan klinički znak u akutnim intoksikacijama benzodiazepinima je poremećaj stanja svesti različitog stepena, blagi u vidu somnolencije, srednje težak kada se opisuje kao sopor, ili težak kada je reč o komi, a kvantitativna procena je vršena pomoću Glasgow Coma Scale (GCS). Procena težine trovanja vršena je u skladu sa Skalom težine trovanja (engl. Poisoning Severity Score, PSS) koja razlikuje četiri stepena težine trovanja, PSS 1, PSS 2, PSS 3 i PSS 4. Rezultati - Studija je pokazala da je stvaranje aktivnih metabolita i metabolički kapacitet manji, a renalna eliminacija sporija, kod osoba starije životne dobi u poređenju sa drugim starosnim grupama. Kod starijih od 65 godina uočena je i češća hipoalbuminemija, što, pored smanjenog ukupnog klirensa, doprinosi dužem održavanju toksičnih koncentracija benzodiazepina. Zbog toga je u grupi pacijenata starijih od 65 godina zabeležena teža i kompleksnija klinička slika (teži i dugotrajniji poremećaji svesti, češći kardiovaskularni poremećaji), duža hospitalizacija, veća potreba za primenom antidota, češće komplikacije (aspiraciona bronhopneumonija i rabdomioliza), oporavak sporiji, a letalitet veći. The aim of this study was to analyze the factors affecting the process of elimination of benzodiazepines, severity of clinical features, complications and outcome of acute poisoning in elderly patients.The study included 95 patients of both genders who were hospitalized in the Department of clinical Toxicology, Military Medical Academy (MMA) in Belgrade. Planned research was performed as a clinical observational cohort study. Patients were divided into three groups according to age (18-40 years old 41 to 65 years, ≥ 65 years of age). All included patients were monitored in accordance wtih the clinical manifestations, as well as the detected toxic concentrations of benzodiazepines in 48 hours period (or until the end of the treatment). In this study, the most common ingested benzodiazepine was bromazepam. Comparing the mean concentration of bromazepam among different age groups, we can see that in the group aged 65 years concentration of drug is slightly higher, but not significantly different compared to younger age groups. The elimination of drug was analyzed by comparing the concentrations of drugs at the admission and by determining the percentage reduction of the concentration after 24 and 48 hours. The hallmark of an acute benzodiazepine intoxication is different level of consciousness disorders that may range from somnolence in mild to coma in severe cases. The Glasgow Coma Scale (GCS) was used to estimate the level of consciousness. Evaluation of the poisoning was performed in accordance with the Poisoning Severity Score, PSS, which differentiate four different degrees of poisoning severity, PSS 1 PSS 2 PSS 3 PSS and PSS 4. Results - The study shows that in group of elderly compared to other age groups, the formation of active metabolites and metabolic capacity decreases and renal elimination is slower. In group of people older than 65 years more common hypoalbuminemia is observed, which, in addition to a reduced total clearance, provides extended maintenance of toxic concentrations of benzodiazepines. Therefore, it is in the group of patients older than 65 years severe and more complex clinical manifestations is observed (deeper and prolonged disorders of consciousness, more common cardiovascular disorders), longer hospital stay, increasing need for antidotes, frequent complications (aspiration bronchopneumonia and rhabdomyolysis), slower recovery and higher lethality. In literature there are studies on the increased susceptibility of the elderly population to the effects of benzodiazepines. However, there is no study that followed the elimination and the clinical effects of benzodiazepines in acute poisoning in the elderly which was the focus of our research. The current findings provide important information and are very useful for effective treatment of the elderly with acute benzodiazepine poisoning. ID=524002453 ; D-3060 91552101 5189 91552100 524002453 2017-08-18T12:42:34.053Z 45 no 46 mentor Nataša, 1967- Perković-Vukčević 2017 63 mentor Jasmina, 1959- Jović-Stošić 2017 63 predsednik komisije Nataša, 1975- Đorđević 2017 63 član komisije Vesela, 1956- Radonjić 2017 63 član komisije Vesna. Mijatović 2017 118 listova 8213933 http://phaidrabg.bg.ac.rs/o:801 no yes 6 2017-08-18T12:42:34.320Z 70 1738 34A05 2017