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 and outcome in elderly people acutely poisoned with benzodiazepines
Докторанд
Perković-Vukčević, NatašaМентор
Jović-Stošić, JasminaЧланови комисије
Đorđević, NatašaRadonjić, Vesela
Mijatović, Vesna
Метаподаци
Приказ свих података о дисертацијиСажетак
Apstrakt:
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.
Abstract
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.