Prescription Opioid Duration of Action and the Risk of Unintentional Overdose Among Patients Receiving Opioid Therapy
Prescription Opioid Duration of Action and the Risk of Unintentional Overdose Among Patients Receiving Opioid Therapy
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DOI：
10.1001/jamainternmed.2014.8071
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发表时间：
2015-04-01
影响因子：
39
通讯作者：
Gagnon, David R.
中科院分区：
文献类型：
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作者：
Miller, Matthew;Barber, Catherine W.;Gagnon, David R.
在过去的20年里，随着处方阿片类药物的销售不断增加，意外过量事件的增加前所未有，这引起了人们对阿片类药物的治疗使用是否导致过量伤害增加的担忧。很少有对照研究调查了阿片类药物处方增加和过量伤害的生态指标在多大程度上反映了服用阿片类药物的患者的风险，更不用说某些阿片类药物方案是否比其他方案更安全。目的探讨非故意过量伤害的风险是否与阿片类药物作用的持续时间有关（即长效与短效制剂）。设计、环境和参与者使用退伍军人管理医疗保健系统的基于人群的医疗保健利用数据进行倾向评分调整队列研究。这些患者是患有慢性疼痛疾病的退伍军人，他们在2000年1月1日至2009年12月31日期间开始使用阿片类镇痛药治疗。使用《国际疾病分类》第九次修订代码明确编码为意外意图（E850.x-860.x）或未确定意图（E980. x）的药物或药物中毒的非故意过量。X或药物中毒[960.x-980]。X]没有伴随的外因伤害代码)。结果共观察到319例非故意用药过量事件。与开始使用短效阿片类药物治疗的患者相比，开始使用长效阿片类药物治疗的患者过量的可能性是其两倍以上。在调整了年龄、性别、阿片类药物剂量和其他临床特征后，长效阿片类药物患者的过量损伤率明显高于短效阿片类药物患者（风险比[HR]， 2.33; 95% CI, 1.26-4.32）。长效药物的相关风险在开始治疗后的前2周尤为明显（HR, 5.25; 1.88-14.72）。结论和相关性据我们所知，本研究的发现提供了第一个证据，表明意外过量伤害的风险与处方阿片类药物的作用时间有关。如果在其他队列中重复，我们的研究结果表明，临床医生在权衡开始不同阿片类药物治疗方案的利弊时，不仅要考虑每日剂量，还要考虑阿片类药物作用的持续时间，尽可能选择短效药物，特别是在治疗的前两周。
IMPORTANCE The unprecedented increase in unintentional overdose events that has occurred in tandem with escalating sales of prescription opioids over the past 2 decades has raised concerns about whether the therapeutic use of opioids has contributed to increases in overdose injury. Few controlled studies have examined the extent to which ecologic measures of increases in opioid prescribing and overdose injuries reflect risk among patients prescribed opioids, let alone whether some opioid regimens are safer than others.OBJECTIVE To examine whether the risk of unintentional overdose injury is associated with the duration of opioid action (ie, long-acting vs short-acting formulations).DESIGN, SETTING, AND PARTICIPANTS A propensity score-adjusted cohort studywas conducted using population-based health care utilization data from the Veterans Administration Healthcare System. The patients were veterans with chronic painful conditions who began therapy with opioid analgesics between January 1, 2000, and December 31, 2009.MAIN OUTCOMES AND MEASURES Unintentional overdoses that are explicitly coded using International Classification of Disease, Ninth Revision codes as drug or medication poisonings of accidental intent (E850.x-860.x) or undetermined intent (E980.x or drug poisoning [960.x-980.x] without an accompanying external cause of injury code).RESULTS A total of 319 unintentional overdose events were observed. Patients initiating therapy with long-acting opioids were more than twice as likely to overdose compared with persons initiating therapy with short-acting opioids. After adjustment for age, sex, opioid dose, and other clinical characteristics, patients receiving long-acting opioids had a significantly higher rate of overdose injury than did those receiving short-acting opioids (hazard ratio [HR], 2.33; 95% CI, 1.26-4.32). The risk associated with long-acting agents was particularly marked during the first 2 weeks after initiation of treatment (HR, 5.25; 1.88-14.72).CONCLUSIONS AND RELEVANCE To our knowledge, the findings of the present study provide the first evidence that the risk of unintentional overdose injury is related to the prescribed opioid's duration of action. If replicated in other cohorts, our findings suggest that clinicians weighing the benefits and risks of initiating different opioid regimens should consider not only the daily dose prescribed but also the duration of opioid action, favoring short-acting agents whenever possible, especially during the first 2 weeks of therapy.