曲马多引起的QTc间期延长：患病率、临床因素及其与血浆浓度的相关性。

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

作者信息

Keller Guillermo A, Etchegoyen María C V, Fernandez Nicolás, Olivera Nancy M, Quiroga Patricia N, Belloso Waldo H, Diez Roberto A, Di Girolamo Guillermo

机构信息

Department of Pharmacology, School of Medicine, University of Buenos Aires, Paraguay 2155 - Piso 16, C1121ABG Ciudad Autónoma de Buenos Aires, Argentina.

出版信息

Curr Drug Saf. 2016;11(3):206-14. doi: 10.2174/1574886311666160225150405.

DOI:10.2174/1574886311666160225150405

PMID:26916784

Abstract

UNLABELLED

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), ΔQTcB 26±40 (-73 to 110), ΔQTcFri 24±48 (-97 to 121), ΔQTcFra 22±42 (-81 to 109) and .QTcH 22±38 (-68 to 110) ms. QTc interval presents high correlation with plasma tramadol concentrations (for .QTc, R>0.77). Renal failure was associated with a relative risk for ΔQTc > 30 ms of 1.90 (IC95% 1.31-2.74) and for ΔQTc > 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.

摘要

未标注

近年来，多起尖端扭转型室速病例与多种阿片类药物有关。然而，目前尚无曲马多相关病例的报道。

目的

评估曲马多在临床环境中对QT间期的影响。

研究设计与方法

对需要使用曲马多进行医疗救助的患者记录其病史和易导致QT间期延长的合并症。在基线和治疗期间进行离子图和心电图检查；使用Bazzet、Fridericia、Framingham和Hogdes公式校正后分析QT间期。

结果

共研究了115例患者（男性占50.4%）。在治疗期间对照时，所有患者均在3.0至5.0天内接受了每日150 - 400毫克的曲马多治疗。曲马多的血浆浓度为201 - 1613纳克/毫升。治疗期间心电图对照结果，以平均值±标准差（范围）表示，显示QTcB为372±32（305至433），QTcFri为356±37（281至429），QTcFra为363±33（299至429），QTcH为362±30（304至427），ΔQTcB为26±40（-73至110），ΔQTcFri为24±48（-97至121），ΔQTcFra为22±42（-81至109），QTcH为22±38（-68至110）毫秒。QTc间期与曲马多血浆浓度高度相关（对于QTc，R>0.77）。肾衰竭与ΔQTc>30毫秒的相对风险为1.90（95%置信区间1.31 - 2.74），与ΔQTc>60毫秒的相对风险为4.74（95%置信区间2.57 - 8.74）相关。在本研究中，没有患者出现心律失常的证据。