Naslov
Clinical trial and pain therapy in critically ill patients.

Autori
Nešković, Nenad

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
Scientific meeting of MAITT

Mjesto i datum
Bikal, Mađarska, 21.09.2018. - 23.09.2018

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Critically ill patients ; Drug metabolism ; Tramadol

Sažetak
Introduction: Survey indicate that almost 80% of patient experience pain and discomfort while in the ICU, and critically ill patients experience pain even more readily then healthy subject. Even pain is a common and distressing symptom in ICU patients yet a major challenge exists in assessing and evaluating the pain. Tramadol is opioid analgesic widely used to treat moderate to severe pain. It is metabolized by cytochrome CYP2D6 in two major metabolites: pharmacologically active metabolite O-desmethyltramadol (M1) and inactive N-desmethyltramadol (M2), respectively. We measured plasma concentrations of tramadol and its major metabolites after usual tramadol doses to investigate the differences in the plasma concentration of tramadol ant its metabolite in the critically ill patients in ICU. Methods: Critically ill patients in ICU received 400 mg tramadol intravenously, divided into 4 doses. Plasma concentrations of tramadol (cT), M1 and M2 were measured 2, 4 and 6 hours after intravenous administration of 100 mg tramadol in 10 patients. Concentrations of tramadol, M1 and M2 were correlated with initial values of albumin, cholinesterase, gamma-glutamyltransferase (GGT) and C-reactive protein (CRP). Further research plan will be described in the lecture. Results: A large individual variations of plasma concentrations of tramadol and its metabolites were registered. Median plasma concentration of cT, M1 and M2 was 354, 23 ug/L (IQR 232, 86 – 449, 75 μg/L), 46, 98 ug/L (IQR 37, 76 – 82, 05 ug/L) and 46, 93 ug/L (IQR 15, 58 – 70, 1 ug/L), respectively. The values of albumin and cholinesterase showed the most pronounced negative correlation with plasma concentrations of M2, although it was not statistically significant (p = 0.122 and p = 0.239, respectively. Conclusion: Large variations of cT, M1 and M2 among patients may be due to CYP2D6 polymorphisms and organ dysfunctions, especially liver dysfunctions in critical ill. A larger sample of patients is required to correlate patient's comorbidities with cT, M1 and M2. Tramadol kinetics in a population of patients undergoing major abdominal surgical procedures, and in patients with a greater or lesser degree of organic failure, is still not well researched. In this lecture, we will discuss the issues we have met so far and our upcoming study will be presented with a work plan, methodology, and potential problem in clinical trial in pain therapy in ICU.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA