曲马多的使用与非癌痛患者低血糖住院风险的关系。

Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain.

机构信息

Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada2Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.

Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada3Department of Oncology, McGill University, Montreal, Quebec, Canada.

出版信息

JAMA Intern Med. 2015 Feb;175(2):186-93. doi: 10.1001/jamainternmed.2014.6512.

DOI:10.1001/jamainternmed.2014.6512

PMID:25485799

Abstract

IMPORTANCE

Tramadol is a weak opioid analgesic whose use has increased rapidly, and it has been associated with adverse events of hypoglycemia.

OBJECTIVE

To assess whether tramadol use, when compared with codeine use, is associated with an increased risk of hospitalization for hypoglycemia.

DESIGN, SETTING, AND PARTICIPANTS: A nested case-control analysis was conducted within the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database of all patients newly treated with tramadol or codeine for noncancer pain between 1998 and 2012. Cohort and case-crossover analyses were also conducted to assess consistency of the results.

MAIN OUTCOMES AND MEASURES

Cases of hospitalization for hypoglycemia were matched with up to 10 controls on age, sex, and duration of follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated comparing use of tramadol with codeine. A cohort analysis, with high-dimensional propensity score-adjusted hazard ratios (HRs) and 95% CIs, was performed comparing tramadol with codeine in the first 30 days after treatment initiation. Finally, a case-crossover analysis was also performed, in which exposure to tramadol in a 30-day risk period immediately before the hospitalization for hypoglycemia was compared with 11 consecutive 30-day control periods. Odds ratios and 95% CIs were estimated using conditional logistic regression analysis.

RESULTS

The cohort included 334,034 patients, of whom 1105 were hospitalized for hypoglycemia during follow-up (incidence, 0.7 per 1000 per year) and matched to 11,019 controls. Compared with codeine, tramadol use was associated with an increased risk of hospitalization for hypoglycemia (OR, 1.52 [95% CI, 1.09-2.10]), particularly elevated in the first 30 days of use (OR, 2.61 [95% CI, 1.61-4.23]). This 30-day increased risk was confirmed in the cohort (HR, 3.60 [95% CI, 1.56-8.34]) and case-crossover analyses (OR, 3.80 [95% CI, 2.64-5.47]).

CONCLUSIONS AND RELEVANCE

The initiation of tramadol therapy is associated with an increased risk of hypoglycemia requiring hospitalization. Additional studies are needed to confirm this rare but potentially fatal adverse event.

摘要

重要性

曲马多是一种弱阿片类镇痛药，其使用量迅速增加，并且与低血糖不良事件有关。

目的

评估与可待因相比，曲马多的使用是否与低血糖住院风险增加相关。

设计、设置和参与者：在英国临床实践研究数据链接与医院发病统计数据库之间进行了嵌套病例对照分析，该数据库纳入了 1998 年至 2012 年间新接受曲马多或可待因治疗非癌症疼痛的所有患者。还进行了队列和病例交叉分析，以评估结果的一致性。

主要结果和措施

将低血糖住院的病例与年龄、性别和随访时间相匹配的多达 10 名对照进行匹配。比较曲马多与可待因使用的比值比（OR）和 95%置信区间（CI）。在治疗开始后 30 天内，使用高维倾向评分调整后的风险比（HR）和 95%CI 进行了队列分析，比较了曲马多与可待因的使用。最后，还进行了病例交叉分析，其中在低血糖住院前的 30 天风险期内暴露于曲马多与 11 个连续的 30 天对照期进行了比较。使用条件逻辑回归分析估计了比值比和 95%CI。

结果

该队列包括 334034 名患者，在随访期间有 1105 人因低血糖住院（发生率为 0.7/1000 人/年），并与 11019 名对照相匹配。与可待因相比，曲马多的使用与低血糖住院风险增加相关（OR，1.52 [95%CI，1.09-2.10]），尤其是在使用的前 30 天（OR，2.61 [95%CI，1.61-4.23]）。这一 30 天的风险增加在队列中得到了证实（HR，3.60 [95%CI，1.56-8.34]）和病例交叉分析（OR，3.80 [95%CI，2.64-5.47]）。