title: Meperidine-induced QTc-interval prolongation: prevalence, risk factors, and correlation to plasma drug and metabolite concentrations .
abstract: 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.
  
  
  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. .
authors: Guillermo Alberto
authors: GA
authors: Keller
authors: María Cecilia
authors: MC
authors: Villa Etchegoyen
authors: Nicolás
authors: N
authors: Fernández
authors: Nancy Mónica
authors: NM
authors: Olivera
authors: Patricia Noemi
authors: PN
authors: Quiroga
authors: Roberto Alejandro
authors: RA
authors: Diez
authors: Guillermo
authors: G
authors: Di Girolamo
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D001118:Argentina / Q000453:epidemiology; D001711:Biotransformation; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D008614:Meperidine / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000453:epidemiology; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000701:Analgesics, Opioid; D008614:Meperidine; C002752:normeperidine