Institute for Health Research, Kaiser Permanente Colorado, Aurora.
Department of Epidemiology, Colorado School of Public Health, Aurora.
JAMA Netw Open. 2019 Apr 5;2(4):e192613. doi: 10.1001/jamanetworkopen.2019.2613.
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.
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.
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).
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.
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.
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.
为了降低过量用药的风险并遵守处方指南而尝试停止阿片类药物治疗，可能会使患者面临阿片类药物剂量变化。即使治疗停止与风险降低相关，这种剂量变化也可能增加阿片类药物过量的风险。
研究阿片类药物剂量变化与阿片类药物过量之间的关联。
设计、设置和参与者：这是一项嵌套病例对照研究，在 2006 年 1 月 1 日至 2018 年 6 月 30 日期间，在科罗拉多州一个大型综合医疗计划和提供系统中进行。队列成员为接受长期阿片类药物治疗的个体。
剂量变化定义为每个患者随访过程中毫克吗啡等效物的标准差，并根据队列中标准差的五分位分布进行分类（0-5.3、5.4-9.1、9.2-14.6、14.7-27.2 和>27.2mg 吗啡等效物）。
使用国际疾病分类，第九修订版和国际疾病分类和相关健康问题，第十修订版代码确定阿片类药物过量病例。每个过量病例患者都使用风险集抽样与多达 20 名对照患者进行匹配。使用条件逻辑回归模型生成匹配的比值比和 95%CI，并根据年龄、性别、种族/民族、药物或酒精使用障碍、吸烟、苯二氮䓬类药物配给、合并症、精神健康障碍、阿片类药物剂量和阿片类药物制剂进行调整。
在接受长期阿片类药物治疗的 14898 名患者（平均[标准差]年龄，56.3[16.0]岁；8988[60.3%]为女性）队列中，228 例阿片类药物过量事件的病例患者与 3547 例对照患者相匹配。病例患者的阿片类药物治疗平均（标准差）持续时间为 36.7（33.7）个月，而对照患者为 33.0（30.9）个月。与低剂量变化相比，高剂量变化（SD>27.2mg 吗啡当量）与过量风险显著增加相关（匹配比值比，3.32；95%CI，1.63-6.77），与阿片类药物剂量无关。
阿片类药物剂量的变化可能是阿片类药物过量的一个风险因素，这表明在管理长期阿片类药物治疗时，从业者应尽量减少剂量变化。
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