Correlation between plasma concentrations of tramadol and its metabolites and the incidence of seizure in tramadol-intoxicated patients

Abstract

Abstract Background: Seizure is one of the important symptoms of tramadol poisoning, but its causes are still unknown. The aim of this study is to find a relationship between tramadol and the concentrations of its metabolites versus the incidence of seizures following the consumption of high doses of tramadol. Methods: For this purpose, the blood samples of 120 tramadol-intoxicated patients were collected. The patients were divided in two groups (seizure and non-seizure). The concentrations of tramadol and its metabolites (M1, M2 and M5) were measured by using a high-performance liquid chromatography method. The relationship between tramadol and the levels of its metabolites and seizure incidences was also investigated. Results: In 72% of the patients, seizures occurred in the first 3 h after the ingestion of tramadol. The seizure incidences were significantly correlated with the patients’ gender, concentrations of tramadol, M1 and M2 and the history of previous seizures (p<0.001). The average concentration of M2 was significantly higher in males (p=0.003). A previous history of the use of sedative-hypnotics and the co-ingestion of benzodiazepines and other opioids were shown to significantly decrease the rate of seizure. The rate of seizure was directly related to the concentrations of tramadol and its metabolites. Higher M2 concentration in males can be considered a reason for increased incidences of seizures in males. The plasma concentration of M1 affected the onset of seizure. Conclusions: Therefore, it can be concluded that differences in the levels of the metabolites can affect the threshold of seizure in tramadol-intoxicated patients.