Karolinska Institutet, Department of Clinical Science and Education at Södersjukhuset, Stockholm, Sweden.
Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
PLoS One. 2019 Apr 17;14(4):e0215356. doi: 10.1371/journal.pone.0215356. eCollection 2019.
Tramadol, a widely used analgesic drug, inhibits the reuptake of noradrenaline and serotonin impairing the aggregation function of thrombocytes. However, the risk for severe bleeding has previously not been studied. The aim of the present study is to investigate the association between tramadol and bleeding peptic ulcer in the Swedish population.
In this register based case-control study based on the Swedish national patient registry and prescription drug registry, we included 18 306 patients hospitalized with a first-time diagnosis of bleeding peptic ulcer. For every case, 4 matched controls were included. To investigate the temporal aspects of tramadol induced bleeding ulcer, exposure was divided into patients with newly initiated and ongoing treatment. To explore a possible confounding by indication, the effect of codeine, a drug also prescribed for the treatment of moderate pain, but not known to affect thrombocyte function, was investigated. Univariable and multivariable logistic regression was used to analyse the association between tramadol use and bleeding ulcer.
Tramadol was associated with an increased risk of bleeding ulcer (adjusted odds ratio (aOR) 2.1, 95% confidence interval: (2.0-2.3). The association was stronger for newly initiated treatment with tramadol 2.8 (2.5-3.2) and weaker for ongoing treatment 1.7 (1.6-1.9). Codeine was also associated with an increased risk of bleeding ulcer 1.9 (1.7-2.1) and this association was also stronger for newly initiated treatment with codeine 2.3 (2.0-2.6) and weaker for ongoing treatment 1.7 (1.5-1.9).
Treatment with tramadol was associated with an increased risk of bleeding peptic ulcer. Most of this association may be mediated by factors related to the pain condition rather than the pharmacologic effect per se.
曲马多是一种广泛使用的镇痛药，它抑制去甲肾上腺素和 5-羟色胺的再摄取，从而损害血小板的聚集功能。然而，其导致严重出血的风险此前尚未得到研究。本研究的目的是在瑞典人群中调查曲马多与出血性消化性溃疡之间的关系。
本基于瑞典全国患者登记处和处方药物登记处的回顾性病例对照研究共纳入了 18306 例首次诊断为出血性消化性溃疡的住院患者。每例病例纳入 4 例匹配对照。为了研究曲马多诱导性出血性溃疡的时间特征，将暴露分为新开始治疗和持续治疗。为了探索潜在的混杂因素，我们还研究了可待因的影响，可待因也是一种用于治疗中度疼痛的药物，但不会影响血小板功能。使用单变量和多变量逻辑回归分析曲马多使用与出血性溃疡之间的关系。
曲马多与出血性溃疡的风险增加相关（调整后的比值比[aOR]2.1，95%置信区间：2.0-2.3）。新开始使用曲马多的风险更高，比值比为 2.8（2.5-3.2），而持续使用的比值比为 1.7（1.6-1.9）。可待因也与出血性溃疡的风险增加相关，比值比为 1.9（1.7-2.1），且新开始使用可待因的风险更高，比值比为 2.3（2.0-2.6），而持续使用的比值比为 1.7（1.5-1.9）。
曲马多治疗与出血性消化性溃疡风险增加相关。这种关联的大部分可能是由与疼痛状况相关的因素介导的，而不是药物本身的药理作用。
