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

Area of Science:

• Cardiology
• Clinical Pharmacology
• Pharmacovigilance

Background:

• Opioids are linked to torsade de pointes, but tramadol's effect on QT interval was previously unreported.
• QT interval prolongation is a critical safety concern for cardiac patients.

Purpose of the Study:

• To investigate the impact of tramadol on the QT interval in a clinical setting.
• To identify risk factors associated with tramadol-induced QT interval changes.

Main Methods:

• 115 patients receiving tramadol (150-400 mg/day) were monitored.
• Electrocardiograms (ECGs) and ionograms were performed at baseline and during treatment.
• QT interval was corrected using standard formulas (Bazett, Fridericia, etc.) and correlated with plasma tramadol levels.

Main Results:

• Tramadol administration showed a significant correlation between plasma concentrations and QT interval prolongation (R>0.77).
• Renal failure was identified as a risk factor, increasing the relative risk for significant QT prolongation (ΔQTc > 30 ms and > 60 ms).
• No cardiac arrhythmias were observed in any patient during the study.

Conclusions:

• Tramadol can cause QT interval prolongation, directly related to plasma drug concentrations.
• Renal impairment is a significant risk factor for both increased tramadol concentration and subsequent QT prolongation.
• While tramadol affects the QT interval, clinical arrhythmia events were not observed in this cohort.