Cohort Study of the Impact of High-Dose Opioid Analgesics on Overdose Mortality
Cohort Study of the Impact of High-Dose Opioid Analgesics on Overdose Mortality
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DOI：
10.1111/pme.12907
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发表时间：
2016-01-01
期刊：
影响因子：
3.1
通讯作者：
Marshall, Steve
中科院分区：
文献类型：
--
作者：
Dasgupta, Nabarun;Funk, Michele Jonsson;Marshall, Steve
目标。以前关于阿片类药物剂量和过量风险的研究以毫克强度为单位提供了有限的粒度，而是依赖于阈值。我们在临床常用剂量的大范围内量化剂量依赖性过量死亡率。我们还研究了苯二氮卓类药物和缓释阿片类药物制剂对死亡率的影响。前瞻性观察队列，随访一年。在一个州（NC）使用受控物质处方监测程序一年，并提供与姓名相关的死亡率数据。北卡罗来纳州居住人口（n = 9,560,234），其中2,182,374名阿片类镇痛药物患者。给暴露者配发固体口服和透皮阿片类镇痛药；使用意向治疗原则计算的人年。结果是阿片类镇痛药主要或辅助作用导致的过量死亡。建立了泊松模型，并利用广义估计方程实现了泊松模型。22.8%的居民配发了阿片类镇痛药。在有执照的临床医生中，89.6%开具阿片类镇痛药，40.0%开具ER制剂。有629例过量死亡，其中一半在死亡当天有有效的阿片类镇痛药处方。在2,182,374名处方阿片类药物的患者中，报告了478例过量死亡（每年0.022%）。在平均每日吗啡当量毫克数范围内，死亡率逐渐上升。80.0%的阿片类镇痛药患者同时使用苯二氮卓类药物。联合配用苯二氮卓类药物和阿片类镇痛药的过量死亡率是单独使用阿片类镇痛药的10倍（7.0 / 10000人年，95% CI: 6.3, 7.8）（0.7 / 10000人年，95% CI: 0.6, 0.9）。患者中剂量依赖的阿片类药物过量风险逐渐增加，并没有显示出明显的风险阈值。迫切需要关于联合用药类别的指导，以便在缓解疼痛和过量用药风险之间取得更好的平衡。
Objective. Previous studies examining opioid dose and overdose risk provide limited granularity by milligram strength and instead rely on thresholds. We quantify dose-dependent overdose mortality over a large spectrum of clinically common doses. We also examine the contributions of benzodiazepines and extended release opioid formulations to mortality.Design. Prospective observational cohort with one year follow-up.Setting. One year in one state (NC) using a controlled substances prescription monitoring program, with name-linked mortality data.Subjects. Residential population of North Carolina (n = 9,560,234), with 2,182,374 opioid analgesic patients.Methods. Exposure was dispensed prescriptions of solid oral and transdermal opioid analgesics; person-years calculated using intent-to-treat principles. Outcome was overdose deaths involving opioid analgesics in a primary or additive role. Poisson models were created, implemented using generalized estimating equations.Results. Opioid analgesics were dispensed to 22.8% of residents. Among licensed clinicians, 89.6% prescribed opioid analgesics, and 40.0% prescribed ER formulations. There were 629 overdose deaths, half of which had an opioid analgesic prescription active on the day of death. Of 2,182,374 patients prescribed opioids, 478 overdose deaths were reported (0.022% per year). Mortality rates increased gradually across the range of average daily milligrams of morphine equivalents. 80.0% of opioid analgesic patients also received benzodiazepines. Rates of overdose death among those co-dispensed benzodiazepines and opioid analgesics were ten times higher (7.0 per 10,000 person-years, 95 percent CI: 6.3, 7.8) than opioid analgesics alone (0.7 per 10,000 person years, 95 percent CI: 0.6, 0.9).Conclusions. Dose-dependent opioid overdose risk among patients increased gradually and did not show evidence of a distinct risk threshold. There is urgent need for guidance about combined classes of medicines to facilitate a better balance between pain relief and overdose risk.