Tramadol Induced QTc-Interval Prolongation: Prevalence, Clinical Factors and Correlation to Plasma Concentrations

In recent years, several cases of torsade de pointes have been associated with many opioids. However, to present no cases have been reported with tramadol. Objective: To evaluate the effect of tramadol on QT-interval in the clinical setting. Research Design and Methods: Medical history and comorbidities predisposing to QT interval prolongation were registered for patients requiring medical assistance that involved tramadol administration. Ionograms and ECGs were performed at baseline and intratreatment; QT interval was analyzed after correction with Bazzet, Fridericia, Framinghan and Hogdes formula. Results: 115 patients were studied (50.4% males) All patients had received tramadol 150-400 mg/day during 3.0-5.0 days at the moment of intratreatment control. Plasma concentrations of tramadol were 201-1613 ng/mL. Intratreatment electrocardiographic control, as mean + SD (range), showed QTcB 372+32 (305 to 433), QTcFri 356+37 (281 to 429), QTcFra 363 +/- 33 (299 to 429), QTcH 362 +/- 30 (304 to 427), Delta QTcB 26 +/- 40 (-73 to 110), Delta QTcFri 24 +/- 48 (-97 to 121), Delta QTcFra 22 +/- 42 (-81 to 109) and Delta QTcH 22 +/- 38 (-68 to 110) ms. QTc interval presents high correlation with plasma tramadol concentrations (for Delta QTc, R>0.77). Renal failure was associated with a relative risk for Delta QTc > 30 ms of 1.90 (IC95% 1.31-2.74) and for Delta QTc > 60 ms of 4.74 (IC95% 2.57-8.74). No patient had evidence of arrhythmia during the present study. Conclusion: Tramadol produces QTc interval prolongation in good correlation with plasma drug concentrations; renal failure is a risk factor for higher concentration and QT prolongation by tramadol.