Meperidine-induced QTc-interval prolongation: prevalence, risk factors, and correlation to plasma drug and metabolite concentrations
| Autor: | Nancy Mónica Olivera, Roberto Alejandro Diez, Guillermo Alberto Keller, Nicolás Fernández, Di Girolamo G, Villa Etchegoyen Mc, Patricia N. Quiroga |
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| Rok vydání: | 2017 |
| Předmět: |
Drug
Male Meperidine Metabolite media_common.quotation_subject Argentina Action Potentials 01 natural sciences QT interval Risk Assessment Correlation 03 medical and health sciences chemistry.chemical_compound Electrocardiography Heart Conduction System Heart Rate Risk Factors Prevalence Medicine Humans Pharmacology (medical) Longitudinal Studies Prospective Studies Renal Insufficiency Biotransformation media_common Aged Pharmacology Aged 80 and over 030504 nursing business.industry 010401 analytical chemistry Middle Aged 0104 chemical sciences Pethidine Analgesics Opioid Long QT Syndrome chemistry Anesthesia Plasma concentration Qtc interval prolongation Female 0305 other medical science business medicine.drug |
| Zdroj: | International journal of clinical pharmacology and therapeutics. 55(3) |
| ISSN: | 0946-1965 |
| Popis: | A prolongation of the QTc-interval has been described for several opioids, including pethidine (meperidine). OBJECTIVE To evaluate in the clinical setting the frequency and risk factors associated with the QT-interval prolongation induced by meperidine. RESEARCH DESIGN AND METHODS We recruited patients requiring meperidine administration and recorded their medical history and comorbidities predisposing to QT-interval prolongation. Ionograms and electrocardiograms (ECGs) were performed at baseline and during treatment; QT was corrected using the Bazzet, Fridericia, Framinghan, and Hogdes formulas. We measured meperidine and normeperidine by gas chromatography. Values are expressed as mean ± SD (range). RESULTS 58 patients were studied (43.1% males). All patients received meperidine at a dose of 304 ± 133 (120 - 480) mg/day. Meperidine and normeperidine concentrations were 369 ± 60 (265 - 519) and 49 ± 17 (15 - 78) ng/mL, respectively. Intratreatment control found QTcB 370 ± 30 (305 - 433), QTcFri 353 ± 35 (281 - 429), QTcFra 360 ± 30 (299 - 429), QTcH 359 ± 27 (304 - 427), ΔQTcB +9 ± 42 (-90 to +136), ΔQTcFri +4 ± 45 (-86 to +137), ΔQTcFra +5 ± 40 (-77 to +129), and ΔQTcH +7 ± 40 (-76 to +129) ms. Meperidine concentration correlated with QTc-interval (R > 0.36) and ΔQTc (R > 0.69) but the correlation was even better for normeperidine concentration, QTc (R > 0.52) and ΔQTc (R > 0.81). Depending on the QTc correction formula used, 13 - 15 patients (22.41 - 25.86%) presented ΔQTc values > 30 ms, and 7 - 8 patients (12.07- 13.79%) showed ΔQTc values > 60 ms. Renal failure was associated with risk for ΔQTc > 30 ms of 3.74 (IC95% 1.73 - 8.10) and for ΔQTc > 60 ms of 4.27 (IC 95% 1.26 - 14.48). No patient developed arrhythmias during the study. CONCLUSIONS Meperidine treatment causes ECG changes (QTc-interval prolongation) in high correlation with normeperidine plasma concentration. Renal failure increases the risk. . |
| Databáze: | OpenAIRE |
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