engleski

Differences in the metabolism of tramadol in critically ill patient in the ICU – pilot study

Introduction: 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 pharmacokinetics of tramadol 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). 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. This poster will show our results and plans for future study.

Analgesia, postoperative ; Pain ; tramadol ; O - demethyltramadol ; N-demethyltramadol ; systemic inflammation

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