Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy
Association Between Opioid Dose Variability and Opioid Overdose Among Adults Prescribed Long-term Opioid Therapy
复制标题
DOI：
10.1001/jamanetworkopen.2019.2613
复制
发表时间：
2019-04-01
影响因子：
13.8
通讯作者：
Xu, Stan
中科院分区：
文献类型：
--
作者：
Glanz, Jason M.;Binswanger, Ingrid A.;Xu, Stan
重要的是，试图停止阿片类药物治疗以降低过量用药的风险，并遵守处方指南，可能会导致患者暴露在阿片类药物剂量的可变性中。这种剂量可变性可能会增加阿片类药物过量的风险，即使停止治疗与降低风险有关。目的研究阿片类药物剂量可变性与阿片类药物过量之间的关系。设计、设置和参与者从2006年1月1日至2018年6月30日，在科罗拉多州一项大型综合健康计划和交付系统中进行了一项嵌套病例对照研究。队列成员是长期服用阿片类药物的个体。剂量变异性被定义为每个患者随访期间吗啡当量毫克的标准偏差，并根据队列中吗啡当量的五分之一分布进行分类(0-5.3，5.4-9.1，9.2-14.6，14.7-27.2和27.2毫克吗啡当量)。主要结果和衡量阿片类药物过量病例根据国际疾病分类第九版和国际疾病和相关健康问题统计分类第十版代码进行识别。使用风险集抽样将每个过量用药的患者与最多20名对照患者进行匹配。应用条件Logistic回归模型，调整年龄、性别、种族/民族、药物或酒精使用障碍、烟草使用、苯二氮卓类药物使用、内科合并症、精神健康障碍、阿片类药物剂量和阿片类药物配方，得到匹配的优势比和95%的CI。结果在14898例患者(平均年龄56.3[16.0]岁；8988例[60.3%]女性)长期服用阿片类药物治疗的队列中，228例发生阿片类药物过量的患者与3547名对照组患者匹配。阿片类药物治疗的平均持续时间，病例组为36.7(33.7)个月，对照组为33.0(30.9)个月。高剂量可变性(SD>；27.2毫克吗啡当量)与低剂量可变性(匹配优势比，3.32；95%可信区间，1.63-6.77)相比，与阿片类药物剂量无关的低剂量可变性(匹配优势比，3.32；95%CI，1.63-6.77)显著增加过量用药的风险。结论阿片类药物剂量的相关性和可变性可能是阿片类药物过量的一个危险因素，建议医生在管理长期阿片类药物治疗时应尽量减少剂量可变性。
IMPORTANCE Attempts to discontinue opioid therapy to reduce the risk of overdose and adhere to prescribing guidelines may lead patients to be exposed to variability in opioid dosing. Such dose variability may increase the risk of opioid overdose even if therapy discontinuation is associated with a reduction in risk.OBJECTIVE To examine the association between opioid dose variability and opioid overdose.DESIGN, SETTING, AND PARTICIPANTS A nested case-control study was conducted in a large Colorado integrated health plan and delivery system from January 1, 2006, through June 30, 2018. Cohort members were individuals prescribed long-term opioid therapy.EXPOSURES Dose variability was defined as the SD of the milligrams of morphine equivalents across each patient's follow-up and categorized based on the quintile distribution of the SD in the cohort (0-5.3, 5.4-9.1, 9.2-14.6, 14.7-27.2, and >27.2 mg of morphine equivalents).MAIN OUTCOMES AND MEASURES Opioid overdose cases were identified using International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Each case patient with overdose was matched to up to 20 control patients using risk set sampling. Conditional logistic regression models were used to generate matched odds ratios and 95% CIs, adjusted for age, sex, race/ethnicity, drug or alcohol use disorder, tobacco use, benzodiazepine dispensings, medical comorbidities, mental health disorder, opioid dose, and opioid formulation.RESULTS In a cohort of 14?898 patients (mean [SD] age, 56.3 [16.0] years; 8988 [60.3%] female) prescribed long-term opioid therapy, 228 case patients with incident opioid overdose were matched to 3547 control patients. The mean (SD) duration of opioid therapy was 36.7 (33.7) months in case patients and 33.0 (30.9) months in control patients. High-dose variability (SD >27.2 mg of morphine equivalents) was associated with a significantly increased risk of overdose compared with low-dose variability (matched odds ratio, 3.32; 95% CI, 1.63-6.77) independent of opioid dose.CONCLUSIONS AND RELEVANCE Variability in opioid dose may be a risk factor for opioid overdose, suggesting that practitioners should seek to minimize dose variability when managing long-term opioid therapy.